P02463 (CO4A1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Collagen alpha-1(IV) chain

Cleaved into the following chain:

1. Arresten

Gene names

Name:

Col4a1

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 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. Arresten, comprising the C-terminal NC1 domain, inhibits angiogenesis and tumor formation. The C-terminal half is found to possess the anti-angiogenic activity. Specifically inhibits endothelial cell proliferation, migration and tube formation. Inhibits expression of hypoxia-inducible factor 1alpha and ERK1/2 and p38 MAPK activation. Ligand for alpha1/beta1 integrin By similarity.
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.
Subcellular location	Secreted › extracellular space › extracellular matrix › basement membrane.
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.
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. 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. Proteolytic processing produces the C-terminal NC1 peptide, arresten By similarity. The trimeric structure of the NC1 domains is stabilized by covalent bonds between Lys and Met residues By similarity.
Disruption phenotype	Mice develop perinatal cerebral hemorrhage and porencephaly. The mutant protein inhibits the secretion of mutant and normal proteins into the basement membrane of embryonic origin. The mutation is semidominant. Ref.13
Sequence similarities	Belongs to the type IV collagen family. Contains 1 collagen IV NC1 (C-terminal non-collagenous) domain.
Sequence caution	The sequence AAH72650.1 differs from that shown. Reason: Frameshift at position 1547. The sequence AAH72650.1 differs from that shown. Reason: Insertion sequence.

Ontologies

Keywords
Biological process	Angiogenesis
Cellular component	Basement membrane Extracellular matrix Secreted
Domain	Collagen Repeat Signal
PTM	Disulfide bond Glycoprotein Hydroxylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW cellular response to amino acid stimulus Inferred from direct assay PubMed 20548288. Source: MGI neuromuscular junction development Inferred from mutant phenotype PubMed 17418794. Source: MGI
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
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27
	Propeptide	28 – 172	145	N-terminal propeptide (7S domain)		PRO_0000005750
	Chain	173 – 1669	1497	Collagen alpha-1(IV) chain		PRO_0000005751
	Chain	1445 – 1669	225	Arresten		PRO_0000390483
Regions
	Domain	1445 – 1669	225	Collagen IV NC1
	Region	173 – 1440	1268	Triple-helical region
Amino acid modifications
	Glycosylation	126	1	N-linked (GlcNAc...) Potential
	Disulfide bond	1460 ↔ 1551		Or C-1460 with C-1548 By similarity
	Disulfide bond	1493 ↔ 1548		Or C-1493 with C-1551 By similarity
	Disulfide bond	1505 ↔ 1511		By similarity
	Disulfide bond	1570 ↔ 1665		Or C-1570 with C-1662 By similarity
	Disulfide bond	1604 ↔ 1662		Or C-1604 with C-1665 By similarity
	Disulfide bond	1616 ↔ 1622		By similarity
	Cross-link	1533		S-Lysyl-methionine sulfilimine (Met-Lys) (interchain with K-1651) By similarity
	Cross-link	1651		S-Lysyl-methionine sulfilimine (Lys-Met) (interchain with M-1533) By similarity
Experimental info
	Sequence conflict	26	1	A → P in CAA29946. Ref.4
	Sequence conflict	186	1	S → L in CAA29946. Ref.4
	Sequence conflict	319	1	Q → S in CAA29946. Ref.4
	Sequence conflict	369	1	Q → L in CAA29946. Ref.4
	Sequence conflict	403	1	L → F in CAA29946. Ref.4
	Sequence conflict	481	1	P → L in CAA29946. Ref.4
	Sequence conflict	493	1	Q → H in CAA29946. Ref.4
	Sequence conflict	621	1	G → S in BAE27208. Ref.2
	Sequence conflict	712	1	S → I in CAA29946. Ref.4
	Sequence conflict	813	1	Q → E in AAA50292. Ref.1
	Sequence conflict	982	1	Q → H in CAA29946. Ref.4
	Sequence conflict	1397	1	V → S in AAA37342. Ref.10

Sequences

	Sequence		Length	Mass (Da)
	P02463 [UniParc]. Last modified February 20, 2007. Version 4. Checksum: EFEEC72AF301E5CF	FASTA	1,669	160,679
	10 20 30 40 50 60 MGPRLSVWLL LLFAALLLHE ERSRAAAKGD CGGSGCGKCD CHGVKGQKGE RGLPGLQGVI 70 80 90 100 110 120 GFPGMQGPEG PHGPPGQKGD AGEPGLPGTK GTRGPPGAAG YPGNPGLPGI PGQDGPPGPP 130 140 150 160 170 180 GIPGCNGTKG ERGPLGPPGL PGFSGNPGPP GLPGMKGDPG EILGHVPGTL LKGERGFPGI 190 200 210 220 230 240 PGMPGSPGLP GLQGPVGPPG FTGPPGPPGP PGPPGEKGQM GSSFQGPKGD KGEQGVSGPP 250 260 270 280 290 300 GVPGQAQVKE KGDFAPTGEK GQKGEPGFPG VPGYGEKGEP GKQGPRGKPG KDGEKGERGS 310 320 330 340 350 360 PGIPGDSGYP GLPGRQGPQG EKGEAGLPGP PGTVIGTMPL GEKGDRGYPG APGLRGEPGP 370 380 390 400 410 420 KGFPGTPGQP GPPGFPTPGQ AGAPGFPGER GEKGDQGFPG VSLPGPSGRD GAPGPPGPPG 430 440 450 460 470 480 PPGQPGHTNG IVECQPGPPG DQGPPGTPGQ PGLTGEVGQK GQKGESCLAC DTEGLRGPPG 490 500 510 520 530 540 PQGPPGEIGF PGQPGAKGDR GLPGRDGLEG LPGPQGSPGL IGQPGAKGEP GEIFFDMRLK 550 560 570 580 590 600 GDKGDPGFPG QPGMPGRAGT PGRDGHPGLP GPKGSPGSIG LKGERGPPGG VGFPGSRGDI 610 620 630 640 650 660 GPPGPPGVGP IGPVGEKGQA GFPGGPGSPG LPGPKGEAGK VVPLPGPPGA AGLPGSPGFP 670 680 690 700 710 720 GPQGDRGFPG TPGRPGIPGE KGAVGQPGIG FPGLPGPKGV DGLPGEIGRP GSPGRPGFNG 730 740 750 760 770 780 LPGNPGPQGQ KGEPGIGLPG LKGQPGLPGI PGTPGEKGSI GGPGVPGEQG LTGPPGLQGI 790 800 810 820 830 840 RGDPGPPGVQ GPAGPPGVPG IGPPGAMGPP GGQGPPGSSG PPGIKGEKGF PGFPGLDMPG 850 860 870 880 890 900 PKGDKGSQGL PGLTGQSGLP GLPGQQGTPG VPGFPGSKGE MGVMGTPGQP GSPGPAGTPG 910 920 930 940 950 960 LPGEKGDHGL PGSSGPRGDP GFKGDKGDVG LPGMPGSMEH VDMGSMKGQK GDQGEKGQIG 970 980 990 1000 1010 1020 PTGDKGSRGD PGTPGVPGKD GQAGHPGQPG PKGDPGLSGT PGSPGLPGPK GSVGGMGLPG 1030 1040 1050 1060 1070 1080 SPGEKGVPGI PGSQGVPGSP GEKGAKGEKG QSGLPGIGIP GRPGDKGDQG LAGFPGSPGE 1090 1100 1110 1120 1130 1140 KGEKGSAGTP GMPGSPGPRG SPGNIGHPGS PGLPGEKGDK GLPGLDGVPG VKGEAGLPGT 1150 1160 1170 1180 1190 1200 PGPTGPAGQK GEPGSDGIPG SAGEKGEQGV PGRGFPGFPG SKGDKGSKGE VGFPGLAGSP 1210 1220 1230 1240 1250 1260 GIPGVKGEQG FMGPPGPQGQ PGLPGTPGHP VEGPKGDRGP QGQPGLPGHP GPMGPPGFPG 1270 1280 1290 1300 1310 1320 INGPKGDKGN QGWPGAPGVP GPKGDPGFQG MPGIGGSPGI TGSKGDMGLP GVPGFQGQKG 1330 1340 1350 1360 1370 1380 LPGLQGVKGD QGDQGVPGPK GLQGPPGPPG PYDVIKGEPG LPGPEGPPGL KGLQGPPGPK 1390 1400 1410 1420 1430 1440 GQQGVTGSVG LPGPPGVPGF DGAPGQKGET GPFGPPGPRG FPGPPGPDGL PGSMGPPGTP 1450 1460 1470 1480 1490 1500 SVDHGFLVTR HSQTTDDPLC PPGTKILYHG YSLLYVQGNE RAHGQDLGTA GSCLRKFSTM 1510 1520 1530 1540 1550 1560 PFLFCNINNV CNFASRNDYS YWLSTPEPMP MSMAPISGDN IRPFISRCAV CEAPAMVMAV 1570 1580 1590 1600 1610 1620 HSQTIQIPQC PNGWSSLWIG YSFVMHTSAG AEGSGQALAS PGSCLEEFRS APFIECHGRG 1630 1640 1650 1660 TCNYYANAYS FWLATIERSE MFKKPTPSTL KAGELRTHVS RCQVCMRRT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The complete primary structure for the alpha 1-chain of mouse collagen IV. Differential evolution of collagen IV domains." Muthukumaran G., Blumberg B., Kurkinen M. J. Biol. Chem. 264:6310-6317(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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]. Strain: C57BL/6 and C57BL/6J. Tissue: Brain, Eye, Heart and Placenta.
[3]	"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]. Strain: C57BL/6 and FVB/N. Tissue: Brain, Colon and Mammary gland.
[4]	"cDNA clones completing the nucleotide and derived amino acid sequence of the alpha 1 chain of basement membrane (type IV) collagen from mouse." Wood L., Theriault N., Vogeli G. FEBS Lett. 227:5-8(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-1154.
[5]	"Structure of the amino-terminal portion of the murine alpha 1(IV) collagen chain and the corresponding region of the gene." Killen P.D., Burbelo P.D., Sakurai Y., Yamada Y. J. Biol. Chem. 263:8706-8709(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-129.
[6]	"Characterization of the promoter for the alpha 1 (IV) collagen gene. DNA sequences within the first intron enhance transcription." Killen P.D., Burbelo P.D., Martin G.R., Yamada Y. J. Biol. Chem. 263:12310-12314(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28.
[7]	"Head-to-head arrangement of murine type IV collagen genes." Kaytes P., Wood L., Theriault N., Kurkinen M., Vogeli G. J. Biol. Chem. 263:19274-19277(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28.
[8]	"Alpha 1(IV) and alpha 2(IV) collagen genes are regulated by a bidirectional promoter and a shared enhancer." Burbelo P.D., Martin G.R., Yamada Y. Proc. Natl. Acad. Sci. U.S.A. 85:9679-9682(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28.
[9]	"Alpha 1 type IV collagen gene evolved differently from fibrillar collagen genes." Sakurai Y., Sullivan M., Yamada Y. J. Biol. Chem. 261:6654-6657(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1110-1135.
[10]	"Isolation of an alpha 1 type-IV collagen cDNA clone using a synthetic oligodeoxynucleotide." Nath P., Laurent M., Horn E., Sobel M.E., Zon G., Vogeli G. Gene 43:301-304(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1149-1424.
[11]	"Amino acid sequence of the non-collagenous globular domain (NC1) of the alpha 1(IV) chain of basement membrane collagen as derived from complementary DNA." Oberbaeumer I., Laurent M., Schwarz U., Sakurai Y., Yamada Y., Vogeli G., Voss T., Siebold B., Glanville R.W., Kuhn K. Eur. J. Biochem. 147:217-224(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1276-1669.
[12]	"Extensive homology between the carboxyl-terminal peptides of mouse alpha 1(IV) and alpha 2(IV) collagen." Kurkinen M., Condon M.R., Blumberg B., Barlow D., Quinones S., Saus J., Pihlajaniemi T. J. Biol. Chem. 262:8496-8499(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1441-1669.
[13]	"Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly." Gould D.B., Phalan F.C., Breedveld G.J., van Mil S.E., Smith R.S., Schimenti J.C., Aguglia U., van der Knaap M.S., Heutink P., John S.W.M. Science 308:1167-1171(2005) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	J04694 mRNA. Translation: AAA50292.1. AK142097 mRNA. Translation: BAE24936.1. AK146487 mRNA. Translation: BAE27208.1. AK147284 mRNA. Translation: BAE27820.1. AK147355 mRNA. Translation: BAE27863.1. AK147661 mRNA. Translation: BAE28055.1. BC002269 mRNA. Translation: AAH02269.1. BC056620 mRNA. Translation: AAH56620.1. BC072650 mRNA. Translation: AAH72650.1. Sequence problems. X06777 mRNA. Translation: CAA29946.1. J03758 mRNA. Translation: AAA37439.1. J03944 Genomic DNA. Translation: AAA37442.1. J04448 Genomic DNA. Translation: AAA37437.1. M23333 Genomic DNA. Translation: AAA51625.1. M12879 Genomic DNA. Translation: AAA37343.1. M13024 Genomic DNA. No translation available. M13025 Genomic DNA. No translation available. M13026 Genomic DNA. Translation: AAA37344.1. M13027 Genomic DNA. Translation: AAA37345.1. M13043 Genomic DNA. Translation: AAA37346.1. M14042 mRNA. Translation: AAA37342.1. X02201 mRNA. Translation: CAA26132.1. M15832 mRNA. Translation: AAA37340.1.
IPI	IPI00109588.
PIR	CGMS4B. A33525.
RefSeq	NP_034061.2. NM_009931.2.
UniGene	Mm.738.
3D structure databases
ProteinModelPortal	P02463.
SMR	P02463. Positions 1442-1669.
ModBase	Search...
PTM databases
PhosphoSite	P02463.
Proteomic databases
PaxDb	P02463.
PRIDE	P02463.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000033898; ENSMUSP00000033898; ENSMUSG00000031502.
GeneID	12826.
KEGG	mmu:12826.
UCSC	uc009kvb.2. mouse.
Organism-specific databases
CTD	1282.
MGI	MGI:88454. Col4a1.
Phylogenomic databases
eggNOG	NOG12793.
GeneTree	ENSGT00690000101772.
HOVERGEN	HBG004933.
InParanoid	P02463.
KO	K06237.
OMA	FAPTGEK.
OrthoDB	EOG45DWPF.
Gene expression databases
Bgee	P02463.
CleanEx	MM_COL4A1.
Genevestigator	P02463.
GermOnline	ENSMUSG00000031502. Mus musculus.
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
NextBio	282314.
SOURCE	Search...

Entry information

Entry name

CO4A1_MOUSE

Accession

Primary (citable) accession number: P02463
Secondary accession number(s): Q3UHJ4 , Q3UJE7, Q3UQV2, Q53X35, Q6GQS7, Q6PHB5, Q99LQ8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	February 20, 2007
Last modified:	May 1, 2013
This is version 128 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program