Q9QZS0 (CO4A3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Collagen alpha-3(IV) chain

Cleaved into the following chain:

1. Tumstatin

Gene names

Name:

Col4a3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1669 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein 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.7 Ref.9 UniProtKB Q01955 Tumstatin, a cleavage fragment corresponding to the collagen alpha 3(IV) NC1 domain, possesses both anti-angiogenic and anti-tumor cell activity; these two anti-tumor properties may be regulated via RGD-independent ITGB3-mediated mechanisms. Ref.3 Ref.7 Ref.9 UniProtKB Q01955
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 promoter, respectively. Interacts with COL4A3BP and ITGB3 By similarity. Associates with LAMB2 at the neuromuscular junction and in GBM. Ref.3 Ref.8 UniProtKB Q01955
Subcellular location	Secreted › extracellular space › extracellular matrix › basement membrane. Note: Colocalizes with COL4A4 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
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 Q01955
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 Q01955 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 Q01955 The trimeric structure of the NC1 domains is stabilized by covalent bonds between Lys and Met residues By similarity. Phosphorylated by the Goodpasture antigen-binding protein/COL4A3BP By similarity. UniProtKB Q01955
Disruption phenotype	Mice exhibit normal pregnancy and wound healing, but consistent with the human hereditary disorder Alport syndrome they develop a progressive glomerulonephritis with microhematuria and proteinuria. Ref.6
Sequence similarities	Belongs to the type IV collagen family. Contains 1 collagen IV NC1 (C-terminal non-collagenous) domain.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Basement membrane Extracellular matrix Secreted
Domain	Collagen Repeat Signal
PTM	Disulfide bond Glycoprotein Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB cell surface receptor signaling pathway Inferred from direct assay Ref.7. Source: UniProtKB glomerular basement membrane development Inferred from mutant phenotype PubMed 12631063. Source: UniProtKB induction of apoptosis Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of angiogenesis Inferred from direct assay Ref.9. Source: UniProtKB
Cellular_component	collagen type IV Inferred from direct assay PubMed 12101409. Source: MGI
Molecular_function	extracellular matrix structural constituent Inferred from electronic annotation. Source: InterPro integrin binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 28	28	Potential
	Chain	29 – 1669	1641	Collagen alpha-3(IV) chain		PRO_0000279698
	Chain	1424 – 1669	246	Tumstatin Ref.3		PRO_0000279699
Regions
	Domain	1444 – 1668	225	Collagen IV NC1
	Region	29 – 42	14	7S domain By similarity UniProtKB Q01955
	Region	43 – 1436	1394	Triple-helical region UniProtKB Q01955
	Region	1425 – 1443	19	Epitope recognized by Goodpasture antibodies By similarity UniProtKB Q01955
	Region	1478 – 1556	79	Required for the anti-angiogenic activity of tumstatin By similarity UniProtKB Q01955
	Region	1609 – 1627	19	Required for the anti-tumor cell activity of tumstatin By similarity UniProtKB Q01955
	Motif	830 – 832	3	Cell attachment site Potential
	Motif	994 – 996	3	Cell attachment site Potential
	Motif	1152 – 1154	3	Cell attachment site Potential
	Motif	1304 – 1306	3	Cell attachment site Potential
Sites
	Site	1424 – 1425	2	Cleavage; by collagenase By similarity UniProtKB Q01955
Amino acid modifications
	Glycosylation	126	1	N-linked (GlcNAc...) Potential
	Glycosylation	253	1	N-linked (GlcNAc...) Potential
	Disulfide bond	1459 ↔ 1550		Or C-1459 with C-1547 By similarity UniProtKB Q01955
	Disulfide bond	1492 ↔ 1547		Or C-1492 with C-1550 By similarity UniProtKB Q01955
	Disulfide bond	1504 ↔ 1510		By similarity UniProtKB Q01955
	Disulfide bond	1569 ↔ 1664		Or C-1569 with C-1661 By similarity UniProtKB Q01955
	Disulfide bond	1603 ↔ 1661		Or C-1603 with C-1664 By similarity UniProtKB Q01955
	Disulfide bond	1615 ↔ 1621		By similarity UniProtKB Q01955
	Cross-link	1412		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
	Cross-link	1532		S-Lysyl-methionine sulfilimine (Met-Lys) (interchain with K-1650) By similarity
	Cross-link	1650		S-Lysyl-methionine sulfilimine (Lys-Met) (interchain with M-1532) By similarity
Experimental info
	Sequence conflict	1041	1	L → R in AAD50449. Ref.1
	Sequence conflict	1594	1	G → R in CAA57689. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q9QZS0 [UniParc]. Last modified March 6, 2007. Version 2. Checksum: 2E976B2F2E66D28E	FASTA	1,669	161,726
	10 20 30 40 50 60 MHSKTAPRFL VFLLLTLLLL LAASPVASKG CVCKGKGQCL CAGTKGEKGE KGVPGSPGFP 70 80 90 100 110 120 GQKGFPGPEG LPGPQGPKGS PGLPGLTGPK GIRGITGLPG FAGPPGLPGL PGHPGPRGLA 130 140 150 160 170 180 GLPGCNGSKG EQGFPGFPGT PGYAGLPGPD GLKGQKGEPA QGEDRGFNGK GDPGPPGVPG 190 200 210 220 230 240 FQGFPGLPGF PGPAGPPGPP GFFGLPGAMG PRGPKGHMGD SVIGQKGERG MKGLTGPPGP 250 260 270 280 290 300 PGTVIFTLTQ PYNKSDFKGE KGDEGERGEP GPPGPSGPPG DSYGSEKGAP GEPGPRGKPG 310 320 330 340 350 360 KDGAPGFPGT EGAKGNRGFP GLRGEAGIKG RKGDIGPPGF PGPTEYYDAY LEKGERGMPG 370 380 390 400 410 420 LPGPKGARGP QGPSGPPGVP GSPGLSRPGL RGPIGWPGLK GSKGERGPPG KDTVGPPGPL 430 440 450 460 470 480 GCPGSPGPPG PPGPPGCPGD IVFKCSPGEH GMPGDTGPPG VPGLDGPKGE PGSPCTECHC 490 500 510 520 530 540 FPGPPGVPGF PGLDGIKGIP GGRGVPGLKG NPGSPGSAGL PGFAGFPGDQ GHPGLKGDKG 550 560 570 580 590 600 DTPLPWGQVG NPGDPGLRGL PGRKGFDGTP GGPGAKGPPG PQGEPALSGR KGDQGPPGPP 610 620 630 640 650 660 GFPGPPGPAG PAGPPGYGPQ GEPGPKGAQG VPGVLGPPGE AGLKGEPSTS TPDLGPPGPP 670 680 690 700 710 720 GPPGQAGPRG LPGLPGPVGK CDPGLPGPDG EPGIPEAGCP GPPGPKGNQG FPGTKGSPGC 730 740 750 760 770 780 PGEMGKPGRP GEPGIPGAKG EPSVGRPGKP GKPGFPGERG NAGENGDIGL PGLPGLPGTP 790 800 810 820 830 840 GRGGLDGPPG DPGQPGSPGA KGSPGRCIPG PRGTQGLPGL NGLKGQPGRR GDTGPKGDPG 850 860 870 880 890 900 IPGMDRSGVP GDPGPPGTPG CPGEMGPPGQ KGYPGAPGFP GPPGEKGEVG MMGYPGTTGP 910 920 930 940 950 960 PGLPGKPGSQ GQRGSLGIPG MKGEKGRPGA KGERGEKGKP GPSQTTLLKG DKGEPGLKGF 970 980 990 1000 1010 1020 VGNPGEKGNR GNPGLPGPKG LEGLPGLPGP PGPRGDTGSR GNPGRPGPHG MPGSMGIMGV 1030 1040 1050 1060 1070 1080 PGPKGRKGTS GLPGLAGRPG LTGIHGPQGD KGEPGYSEGA RPGPPGPKGD PGLPGDKGKK 1090 1100 1110 1120 1130 1140 GERGVPGPPG QSGPAGPDGA PGSPGSPGHP GKPGPAGDLG LKGQKGFPGP PGSTGPPGPP 1150 1160 1170 1180 1190 1200 GLPGLPGPMG MRGDQGRDGI PGPPGEKGET GLLGAYPGPK GSPGVPGAKG DRGVPGLSGL 1210 1220 1230 1240 1250 1260 PGRKGVMGDV GPQGPPGTAG LPGPPGLPGA IIPGPKGDRG LPGLRGNPGE PGPPGPPGPI 1270 1280 1290 1300 1310 1320 GKGIKGDKGF MGPPGPKGLP GTVGDMGPPG FPGAPGTPGL PGVRGDPGFP GFPGIKGEKG 1330 1340 1350 1360 1370 1380 NPGFLGPIGH PGPVGPKGPP GPRGKPGTLK VISLPGSPGP PGVPGQPGMK GDPGPLGLPG 1390 1400 1410 1420 1430 1440 IPGPCGPRGK PGKDGKPGTP GPAGTKGNKG LKGQQGPPGL DGLPGLKGNP GDRGTPATGT 1450 1460 1470 1480 1490 1500 RMRGFIFTRH SQTTAIPSCP EGTQPLYSGF SLLFVQGNKR AHGQDLGTLG SCLQRFTTMP 1510 1520 1530 1540 1550 1560 FLFCNINNVC NFASRNDYSY WLSTPALMPM DMAPISGRAL EPYISRCTVC EGPAMAIAVH 1570 1580 1590 1600 1610 1620 SQTTAIPPCP QDWVSLWKGF SFIMFTSAGS EGAGQALASP GSCLEEFRAS PFIECHGRGT 1630 1640 1650 1660 CNYYSNSYSF WLASLNPERM FRKPIPSTVK AGDLEKIISR CQVCMKKRH

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Embryonic kidney.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[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 1424-1669, FUNCTION, INTERACTION WITH LAMB2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Strain: BALB/c. Tissue: Kidney.
[4]	"Cloning of the NC1 domains fo the minor collagen IV chains of mouse via PCR (RACE) reveals the presence of the mRNAs for alpha3 (IV) and alpha5 (IV) in differentiated teratocarcinoma cells." Oberbaeumer I. Submitted (OCT-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1491-1651. Strain: 129. Tissue: Epithelium.
[5]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1558-1669. Strain: C57BL/6J. Tissue: Embryonic lung.
[6]	"Collagen COL4A3 knockout: a mouse model for autosomal Alport syndrome." Cosgrove D., Meehan D.T., Grunkemeyer J.A., Kornak J.M., Sayers R., Hunter W.J., Samuelson G.C. Genes Dev. 10:2981-2992(1996) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[7]	"Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin." Hamano Y., Zeisberg M., Sugimoto H., Lively J.C., Maeshima Y., Yang C., Hynes R.O., Werb Z., Sudhakar A., Kalluri R. Cancer Cell 3:589-601(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Characterization of assembly of recombinant type IV collagen alpha3, alpha4, and alpha5 chains in transfected cell strains." Kobayashi T., Uchiyama M. Kidney Int. 64:1986-1996(2003) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH COL4A4 AND COL4A5.
[9]	"Tumor-specific expression of the RGD-alpha3(IV)NC1 domain suppresses endothelial tube formation and tumor growth in mice." Miyoshi T., Hirohata S., Ogawa H., Doi M., Obika M., Yonezawa T., Sado Y., Kusachi S., Kyo S., Kondo S., Shiratori Y., Hudson B.G., Ninomiya Y. FASEB J. 20:1904-1906(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF169387 mRNA. Translation: AAD50449.1. AC123746 Genomic DNA. No translation available. AC138214 Genomic DNA. No translation available. Z35166 mRNA. Translation: CAA84529.1. X82205 mRNA. Translation: CAA57689.1. AK033387 mRNA. Translation: BAC28260.1.
IPI	IPI00137938.
PIR	I48302. S49488.
RefSeq	NP_031760.2. NM_007734.2.
UniGene	Mm.389135.
3D structure databases
HSSP	HSSP built from PDB template 1M3D based on UniProtKB Q7SIB2.
ProteinModelPortal	Q9QZS0.
SMR	Q9QZS0. Positions 1444-1667.
ModBase	Search...
PTM databases
PhosphoSite	Q9QZS0.
Proteomic databases
PaxDb	Q9QZS0.
PRIDE	Q9QZS0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000113457; ENSMUSP00000109084; ENSMUSG00000079465.
GeneID	12828.
KEGG	mmu:12828.
UCSC	uc007brv.1. mouse.
Organism-specific databases
CTD	1285.
MGI	MGI:104688. Col4a3.
Phylogenomic databases
eggNOG	NOG12793.
GeneTree	ENSGT00690000101772.
HOGENOM	HOG000085652.
HOVERGEN	HBG004933.
InParanoid	Q9QZS0.
KO	K06237.
OMA	GMRGNQG.
OrthoDB	EOG42JNQS.
Gene expression databases
ArrayExpress	Q9QZS0.
Bgee	Q9QZS0.
CleanEx	MM_COL4A3.
Genevestigator	Q9QZS0.
Family and domain databases
Gene3D	2.170.240.10. 1 hit.
InterPro	IPR016187. C-type_lectin_fold. IPR008160. Collagen. IPR001442. Collagen_VI_NC. [Graphical view]
Pfam	PF01413. C4. 2 hits. PF01391. Collagen. 20 hits. [Graphical view]
SMART	SM00111. C4. 2 hits. [Graphical view]
SUPFAM	SSF56436. C-type_lectin_fold. 2 hits.
PROSITE	PS51403. NC1_IV. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	COL4A3. mouse.
NextBio	282322.
SOURCE	Search...

Entry information

Entry name

CO4A3_MOUSE

Accession

Primary (citable) accession number: Q9QZS0
Secondary accession number(s): Q61430, Q61435, Q8CCD6

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 6, 2007
Last sequence update:	March 6, 2007
Last modified:	May 1, 2013
This is version 90 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program