P08122 (CO4A2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Collagen alpha-2(IV) chain

Cleaved into the following chain:

1. Canstatin

Gene names

Name:

Col4a2

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	1707 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.10 Canstatin, a cleavage product corresponding to the collagen alpha 2(IV) NC1 domain, possesses both anti-angiogenic and anti-tumor cell activity. It inhibits proliferation and migration of endothelial cells, reduces mitochondrial membrane potential, and induces apoptosis. Specifically induces Fas-dependent apoptosis and activates procaspase-8 and -9 activity. Ligand for alphavbeta3 and alphavbeta5 integrins By similarity. Ref.10
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 By similarity.
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, canstatin By similarity. The trimeric structure of the NC1 domains is stabilized by covalent bonds between Lys and Met residues By similarity.
Sequence similarities	Belongs to the type IV collagen family. Contains 1 collagen IV NC1 (C-terminal non-collagenous) domain.
Sequence caution	The sequence AAH80789.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence starting in position 277. The sequence AAI07686.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence starting in position 277.

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 transforming growth factor beta stimulus Inferred from expression pattern PubMed 17525254. Source: UniProtKB negative regulation of angiogenesis Inferred from sequence or structural similarity. Source: UniProtKB transcription, DNA-dependent Inferred from direct assay PubMed 17525254. 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
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25
	Propeptide	26 – 183	158	N-terminal propeptide (7S domain)		PRO_0000005826
	Chain	184 – 1707	1524	Collagen alpha-2(IV) chain		PRO_0000005827
	Chain	1481 – 1707	227	Canstatin		PRO_0000390487
Regions
	Domain	1484 – 1707	224	Collagen IV NC1
	Region	184 – 1479	1296	Triple-helical region
Amino acid modifications
	Glycosylation	138	1	N-linked (GlcNAc...) Potential
	Glycosylation	1270	1	N-linked (GlcNAc...) Potential
	Disulfide bond	1499 ↔ 1588		By similarity
	Disulfide bond	1532 ↔ 1585		By similarity
	Disulfide bond	1544 ↔ 1550		By similarity
	Disulfide bond	1607 ↔ 1703		By similarity
	Disulfide bond	1641 ↔ 1700		By similarity
	Disulfide bond	1653 ↔ 1660		By similarity
Experimental info
	Sequence conflict	275	1	E → K in AAH80789. Ref.3
	Sequence conflict	626	1	E → R in AAA50293. Ref.1
	Sequence conflict	837	1	G → A in AAA50293. Ref.1
	Sequence conflict	1051	1	P → R in CAA27998. Ref.8
	Sequence conflict	1097	1	S → G in CAA26655. Ref.6
	Sequence conflict	1171	1	G → S in CAA27998. Ref.8
	Sequence conflict	1179	1	P → R in CAA27998. Ref.8
	Sequence conflict	1241	1	Q → E in CAA27998. Ref.8
	Sequence conflict	1328	1	P → A in CAA27998. Ref.8
	Sequence conflict	1573	1	V → L in CAA28308. Ref.9
	Sequence conflict	1583	1	S → I in AAR89902. Ref.11
	Sequence conflict	1583	1	S → I in AAQ83370. Ref.11
	Sequence conflict	1623	1	H → Y in AAA50293. Ref.1
	Sequence conflict	1623	1	H → Y in AAA37341. Ref.10

Sequences

	Sequence		Length	Mass (Da)
	P08122 [UniParc]. Last modified February 20, 2007. Version 4. Checksum: 67CB3E3CB2A5B1F6	FASTA	1,707	167,325
	10 20 30 40 50 60 MDRVRFKASG PPLRGWLLLA TVTVGLLAQS VLGGVKKLDV PCGGRDCSGG CQCYPEKGAR 70 80 90 100 110 120 GQPGAVGPQG YNGPPGLQGF PGLQGRKGDK GERGVPGPTG PKGDVGARGV SGFPGADGIP 130 140 150 160 170 180 GHPGQGGPRG RPGYDGCNGT RGDAGPQGPS GSGGFPGLPG PQGPKGQKGE PYALSKEDRD 190 200 210 220 230 240 KYRGEPGEPG LVGYQGPPGR PGPIGQMGPM GAPGRPGPPG PPGPKGQPGN RGLGFYGQKG 250 260 270 280 290 300 EKGDIGQPGP NGIPSDITLV GPTTSTIHPD LYKGEKGDEG EQGIPGVISK GEEGIMGFPG 310 320 330 340 350 360 IRGFPGLDGE KGVVGQKGSR GLDGFQGPSG PRGPKGERGE QGPPGPSVYS PHPSLAKGAR 370 380 390 400 410 420 GDPGFQGAHG EPGSRGEPGE PGTAGPPGPS VGDEDSMRGL PGEMGPKGFS GEPGSPARYL 430 440 450 460 470 480 GPPGADGRPG PQGVPGPAGP PGPDGFLFGL KGSEGRVGYP GPSGFPGTRG QKGWKGEAGD 490 500 510 520 530 540 CQCGQVIGGL PGLPGPKGFP GVNGELGKKG DQGDPGLHGI PGFPGFKGAP GVAGAPGPKG 550 560 570 580 590 600 IKGDSRTITT KGERGQPGIP GVHGMKGDDG VPGRDGLDGF PGLPGPPGDG IKGPPGDAGL 610 620 630 640 650 660 PGVPGTKGFP GDIGPPGQGL PGPKGERGFP GDAGLPGPPG FPGPPGPPGT PGQRDCDTGV 670 680 690 700 710 720 KRPIGGGQQV VVQPGCIEGP TGSPGQPGPP GPTGAKGVRG MPGFPGASGE QGLKGFPGDP 730 740 750 760 770 780 GREGFPGPPG FMGPRGSKGT TGLPGPDGPP GPIGLPGPAG PPGDRGIPGE VLGAQPGTRG 790 800 810 820 830 840 DAGLPGQPGL KGLPGETGAP GFRGSQGMPG MPGLKGQPGF PGPSGQPGQS GPPGQHGFPG 850 860 870 880 890 900 TPGREGPLGQ PGSPGLGGLP GDRGEPGDPG VPGPVGMKGL SGDRGDAGMS GERGHPGSPG 910 920 930 940 950 960 FKGMAGMPGI PGQKGDRGSP GMDGFQGMLG LKGRQGFPGT KGEAGFFGVP GLKGLPGEPG 970 980 990 1000 1010 1020 VKGNRGDRGP PGPPPLILPG MKDIKGEKGD EGPMGLKGYL GLKGIQGMPG VPGVSGFPGL 1030 1040 1050 1060 1070 1080 PGRPGFIKGV KGDIGVPGTP GLPGFPGVSG PPGITGFPGF TGSRGEKGTP GVAGVFGETG 1090 1100 1110 1120 1130 1140 PTGDFGDIGD TVDLPGSPGL KGERGITGIP GLKGFFGEKG AAGDIGFPGI TGMAGAQGSP 1150 1160 1170 1180 1190 1200 GLKGQTGFPG LTGLQGPQGE PGRIGIPGDK GDFGWPGVPG LPGFPGIRGI SGLHGLPGTK 1210 1220 1230 1240 1250 1260 GFPGSPGVDA HGDPGFPGPT GDRGDRGEAN TLPGPVGVPG QKGERGTPGE RGPAGSPGLQ 1270 1280 1290 1300 1310 1320 GFPGISPPSN ISGSPGDVGA PGIFGLQGYQ GPPGPPGPNA LPGIKGDEGS SGAAGFPGQK 1330 1340 1350 1360 1370 1380 GWVGDPGPQG QPGVLGLPGE KGPKGEQGFM GNTGPSGAVG DRGPKGPKGD QGFPGAPGSM 1390 1400 1410 1420 1430 1440 GSPGIPGIPQ KIAVQPGTLG PQGRRGLPGA LGEIGPQGPP GDPGFRGAPG KAGPQGRGGV 1450 1460 1470 1480 1490 1500 SAVPGFRGDQ GPMGHQGPVG QEGEPGRPGS PGLPGMPGRS VSIGYLLVKH SQTDQEPMCP 1510 1520 1530 1540 1550 1560 VGMNKLWSGY SLLYFEGQEK AHNQDLGLAG SCLARFSTMP FLYCNPGDVC YYASRNDKSY 1570 1580 1590 1600 1610 1620 WLSTTAPLPM MPVAEEEIKP YISRCSVCEA PAVAIAVHSQ DTSIPHCPAG WRSLWIGYSF 1630 1640 1650 1660 1670 1680 LMHTAAGDEG GGQSLVSPGS CLEDFRATPF IECNGGRGTC HYFANKYSFW LTTIPEQNFQ 1690 1700 STPSADTLKA GLIRTHISRC QVCMKNL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The complete primary structure of mouse alpha 2(IV) collagen. Alignment with mouse alpha 1(IV) collagen." Saus J., Quinones S., Mackrell A., Blumberg B., Muthukumaran G., Pihlajaniemi T., Kurkinen M. J. Biol. Chem. 264:6318-6324(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] OF 1-538 AND 1649-1707. Strain: C57BL/6J. Tissue: Eye and Spinal cord.
[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] OF 1-276 AND 1339-1707. Tissue: Mammary gland.
[4]	"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 / MRNA] OF 1-60.
[5]	"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 1-33.
[6]	"Characterization of 64-, 123- and 182-base-pair exons in the mouse alpha 2(IV) collagen gene." Kurkinen M., Bernard M.P., Barlow D.P., Chow L.T. Nature 317:177-179(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 964-1003; 1005-1085 AND 1087-1109.
[7]	"Structure of mouse type IV collagen. Amino-acid sequence of the C-terminal 511-residue-long triple-helical segment of the alpha 2(IV) chain and its comparison with the alpha 1(IV) chain." Schwarz U., Schuppan D., Oberbaeumer I., Glanville R.W., Deutzmann R., Timpl R., Kuehn K. Eur. J. Biochem. 157:49-56(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 970-1480.
[8]	"Proposed alignment of helical interruptions in the two subunits of the basement membrane (type IV) collagen." Vogeli G., Horn E., Carter J., Kaytes P.S. FEBS Lett. 206:29-32(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1041-1489.
[9]	"cDNA and protein sequence of the NC1 domain of the alpha 2-chain of collagen IV and its comparison with alpha 1(IV)." Schwarz-Magdolen U., Oberbaeumer I., Kuehn K. FEBS Lett. 208:203-207(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1480-1707.
[10]	"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 1481-1707, FUNCTION OF CANSTATIN.
[11]	"Recombinant mouse canstatin inhibits chicken embryo chorioallantoic membrane angiogenesis and endothelial cell proliferation." Hou W.H., Wang T.Y., Yuan B.M., Chai Y.R., Jia Y.L., Tian F., Wang J.M., Xue L.X. Acta Biochim. Biophys. Sin. 36:845-850(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1481-1707. Strain: BALB/c.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	J04695 mRNA. Translation: AAA50293.1. AK053858 mRNA. Translation: BAC35559.1. AK075619 mRNA. Translation: BAC35863.1. AK164096 mRNA. Translation: BAE37626.1. BC013560 mRNA. Translation: AAH13560.2. BC080789 mRNA. Translation: AAH80789.1. Sequence problems. BC107685 mRNA. Translation: AAI07686.1. Sequence problems. M23334, M23333 Genomic DNA. Translation: AAA51626.1. J04448 Genomic DNA. Translation: AAA37438.1. X02896 mRNA. Translation: CAA26655.1. X02897 Genomic DNA. Translation: CAB51614.1. X02898 Genomic DNA. Translation: CAA26657.1. X02899 Genomic DNA. Translation: CAA26658.1. X04410 mRNA. Translation: CAA27998.1. X04647 mRNA. Translation: CAA28308.1. M15833 mRNA. Translation: AAA37341.1. AY375463 mRNA. Translation: AAQ83370.1. AY502946 mRNA. Translation: AAR89901.1. AY502947 mRNA. Translation: AAR89902.1.
IPI	IPI00338452.
PIR	A33526.
RefSeq	NP_034062.3. NM_009932.3.
UniGene	Mm.181021.
3D structure databases
ProteinModelPortal	P08122.
SMR	P08122. Positions 1482-1706.
ModBase	Search...
PTM databases
PhosphoSite	P08122.
Proteomic databases
PaxDb	P08122.
PRIDE	P08122.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000033899; ENSMUSP00000033899; ENSMUSG00000031503.
GeneID	12827.
KEGG	mmu:12827.
UCSC	uc009kvc.2. mouse.
Organism-specific databases
CTD	1284.
MGI	MGI:88455. Col4a2.
Phylogenomic databases
eggNOG	NOG12793.
GeneTree	ENSGT00690000101772.
HOVERGEN	HBG004933.
InParanoid	P08122.
KO	K06237.
OMA	TTIPEQN.
OrthoDB	EOG4XGZZF.
Gene expression databases
ArrayExpress	P08122.
Bgee	P08122.
CleanEx	MM_COL4A2.
Genevestigator	P08122.
GermOnline	ENSMUSG00000031503. 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. 19 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	COL4A2. mouse.
NextBio	282318.
SOURCE	Search...

Entry information

Entry name

CO4A2_MOUSE

Accession

Primary (citable) accession number: P08122
Secondary accession number(s): Q3B7C2 , Q3TPV9, Q61375, Q66JS5, Q6RCT6, Q6RCT7, Q6U9X1, Q8BPI9, Q8BPK3, Q91VI3

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	February 20, 2007
Last modified:	May 29, 2013
This is version 138 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program