P02462 (CO4A1_HUMAN) 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

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

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.12 Ref.17 Ref.18 Ref.19 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. Ref.12 Ref.17 Ref.18 Ref.19
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.
Tissue specificity	Highly expressed in placenta. Ref.12 Ref.17
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	Lysines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in all cases and bind carbohydrates. 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. The trimeric structure of the NC1 domains is stabilized by covalent bonds between Lys and Met residues. Proteolytic processing produces the C-terminal NC1 peptide, arresten.
Involvement in disease	Brain small vessel disease with hemorrhage (BSVDH) [MIM:607595]: Brain small vessel diseases underlie 20 to 30 percent of ischemic strokes and a larger proportion of intracerebral hemorrhages. Inheritance is autosomal dominant. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.23 Ref.24 Ref.27 Ref.30 Ref.31 Hereditary angiopathy with nephropathy aneurysms and muscle cramps (HANAC) [MIM:611773]: The clinical renal manifestations include hematuria and bilateral large cysts. Histologic analysis revealed complex basement membrane defects in kidney and skin. The systemic angiopathy appears to affect both small vessels and large arteries. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.25 Ref.29 Porencephaly 1 (POREN1) [MIM:175780]: A neurologic disorder characterized by a fluid-filled cysts or cavities within the cerebral hemispheres, neurologic manifestations, facial paresis, and visual defects. Affected individuals typically have hemiplegia, seizures, and intellectual disability. Porencephaly type 1 is usually unilateral and results from focal destructive lesions such as fetal vascular occlusion or birth trauma. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.21 Ref.22 Ref.28
Sequence similarities	Belongs to the type IV collagen family. Contains 1 collagen IV NC1 (C-terminal non-collagenous) domain.

Ontologies

Keywords
Biological process	Angiogenesis
Cellular component	Basement membrane Extracellular matrix Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Collagen Repeat Signal
PTM	Disulfide bond Glycoprotein Hydroxylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW axon guidance Traceable author statement. Source: Reactome cellular response to amino acid stimulus Inferred from electronic annotation. Source: Compara collagen catabolic process Traceable author statement. Source: Reactome extracellular matrix disassembly Traceable author statement. Source: Reactome neuromuscular junction development Inferred from electronic annotation. Source: Compara
Cellular_component	collagen type IV Inferred from electronic annotation. Source: Compara endoplasmic reticulum lumen Traceable author statement. Source: Reactome extracellular region Non-traceable author statement PubMed 14718574. Source: UniProtKB
Molecular_function	extracellular matrix structural constituent Inferred from electronic annotation. Source: InterPro platelet-derived growth factor binding Inferred from direct assay PubMed 8900172. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
COL4A2	P08572	2	EBI-2432478,EBI-2432506

Alternative products

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

Isoform 1 (identifier: P02462-1)

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 (identifier: P02462-2)

The sequence of this isoform differs from the canonical sequence as follows:
     498-848: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 27

27

Ref.6

Propeptide

28 – 172

145

N-terminal propeptide (7S domain)

PRO_0000005748

Chain

173 – 1669

1497

Collagen alpha-1(IV) chain

PRO_0000005749

Chain

1445 – 1669

225

Arresten

PRO_0000390482

Regions

Domain

1445 – 1669

225

Collagen IV NC1

Region

173 – 1440

1268

Triple-helical region

Amino acid modifications

Glycosylation

126

1

N-linked (GlcNAc...)

Disulfide bond

1460 ↔ 1551

Ref.11

Disulfide bond

1493 ↔ 1548

Ref.11

Disulfide bond

1505 ↔ 1511

Ref.11

Disulfide bond

1570 ↔ 1665

Ref.11

Disulfide bond

1604 ↔ 1662

Ref.11

Disulfide bond

1616 ↔ 1622

Ref.11

Cross-link

1533

S-Lysyl-methionine sulfilimine (Met-Lys) (interchain with K-1651)

Cross-link

1651

S-Lysyl-methionine sulfilimine (Lys-Met) (interchain with M-1533)

Natural variations

Alternative sequence

498 – 848

351

Missing in isoform 2.

VSP_034644

Natural variant

7

1

V → L. Ref.32
Corresponds to variant rs9515185 [ dbSNP | Ensembl ].

VAR_030027

Natural variant

304

1

P → L.
Corresponds to variant rs34843786 [ dbSNP | Ensembl ].

VAR_044158

Natural variant

498

1

G → R in HANAC. Ref.29

VAR_064493

Natural variant

498

1

G → V in HANAC. Ref.25

VAR_044159

Natural variant

510

1

G → R in HANAC. Ref.29

VAR_064494

Natural variant

519

1

G → R in HANAC. Ref.25

VAR_044160

Natural variant

525

1

G → L in HANAC; requires 2 nucleotide substitutions. Ref.29

VAR_064495

Natural variant

528

1

G → E in HANAC. Ref.25

VAR_044161

Natural variant

555

1

T → P. Ref.1 Ref.3 Ref.4 Ref.7 Ref.32
Corresponds to variant rs536174 [ dbSNP | Ensembl ].

VAR_030511

Natural variant

562

1

G → E in BSVDH. Ref.23

VAR_030028

Natural variant

720

1

G → D in BSVDH; diffuse small vessel disease of the brain associated with Axenfeld-Rieger anomaly and leukoencephalopathy. Ref.24 Ref.30

VAR_064496

Natural variant

749

1

G → S in POREN1. Ref.21

VAR_030029

Natural variant

755

1

G → R in BSVDH; associated with ocular anomalies of variable severity in some patients. Ref.30 Ref.31

VAR_064497

Natural variant

805

1

G → R in BSVDH. Ref.27

VAR_064498

Natural variant

1130

1

G → D in POREN1. Ref.22

VAR_030030

Natural variant

1236

1

G → R in POREN1. Ref.21

VAR_030031

Natural variant

1334

1

Q → H. Ref.3 Ref.32
Corresponds to variant rs3742207 [ dbSNP | Ensembl ].

VAR_020013

Natural variant

1423

1

G → R in POREN1. Ref.22

VAR_030032

Natural variant

1580

1

G → R in POREN1. Ref.28

VAR_064499

Experimental info

Sequence conflict

237 – 238

2

SG → KE AA sequence Ref.6

Sequence conflict

241

1

G → K AA sequence Ref.6

Sequence conflict

319

1

Q → A in CAA29075. Ref.4

Sequence conflict

719

1

N → D AA sequence Ref.8

Sequence conflict

837

1

D → Y AA sequence Ref.8

Sequence conflict

842

1

K → P AA sequence Ref.8

Sequence conflict

896

1

V → W in CAA68698. Ref.7

Sequence conflict

904

1

E → Q AA sequence Ref.8

Sequence conflict

914

1

S → K AA sequence Ref.8

Sequence conflict

998

1

S → K AA sequence Ref.8

Sequence conflict

1010

1

K → P AA sequence Ref.8

Sequence conflict

1012

1

S → K AA sequence Ref.8

Sequence conflict

1358

1

E → Q AA sequence Ref.8

Sequence conflict

1490

1

A → T in ABE73157. Ref.17

Sequence conflict

1507

1

I → T in ABE73157. Ref.17

Sequence conflict

1519

1

Y → C in ABE73157. Ref.17

Sequence conflict

1570

1

C → Y in AAM97359. Ref.16

Secondary structure

1

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1669

Helix Strand Turn

Details...

Beta strand

1446 – 1451

6

Beta strand

1453 – 1456

4

Beta strand

1465 – 1478

14

Beta strand

1481 – 1484

4

Helix

1490 – 1492

3

Beta strand

1493 – 1496

4

Beta strand

1502 – 1505

4

Beta strand

1509 – 1514

6

Beta strand

1519 – 1524

6

Helix

1538 – 1544

7

Beta strand

1547 – 1555

9

Beta strand

1557 – 1561

5

Beta strand

1563 – 1566

4

Beta strand

1574 – 1587

14

Helix

1589 – 1591

3

Beta strand

1593 – 1595

3

Helix

1601 – 1603

3

Beta strand

1604 – 1607

4

Beta strand

1613 – 1617

5

Beta strand

1620 – 1623

4

Beta strand

1629 – 1634

6

Helix

1638 – 1640

3

Beta strand

1648 – 1651

4

Helix

1655 – 1658

4

Beta strand

1661 – 1667

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 6, 2007. Version 3. Checksum: 3C9BCD8E410A9ED1	FASTA	1,669	160,615
	10 20 30 40 50 60 MGPRLSVWLL LLPAALLLHE EHSRAAAKGG CAGSGCGKCD CHGVKGQKGE RGLPGLQGVI 70 80 90 100 110 120 GFPGMQGPEG PQGPPGQKGD TGEPGLPGTK GTRGPPGASG YPGNPGLPGI PGQDGPPGPP 130 140 150 160 170 180 GIPGCNGTKG ERGPLGPPGL PGFAGNPGPP GLPGMKGDPG EILGHVPGML LKGERGFPGI 190 200 210 220 230 240 PGTPGPPGLP GLQGPVGPPG FTGPPGPPGP PGPPGEKGQM GLSFQGPKGD KGDQGVSGPP 250 260 270 280 290 300 GVPGQAQVQE KGDFATKGEK GQKGEPGFQG MPGVGEKGEP GKPGPRGKPG KDGDKGEKGS 310 320 330 340 350 360 PGFPGEPGYP GLIGRQGPQG EKGEAGPPGP PGIVIGTGPL GEKGERGYPG TPGPRGEPGP 370 380 390 400 410 420 KGFPGLPGQP GPPGLPVPGQ AGAPGFPGER GEKGDRGFPG TSLPGPSGRD GLPGPPGSPG 430 440 450 460 470 480 PPGQPGYTNG IVECQPGPPG DQGPPGIPGQ PGFIGEIGEK GQKGESCLIC DIDGYRGPPG 490 500 510 520 530 540 PQGPPGEIGF PGQPGAKGDR GLPGRDGVAG VPGPQGTPGL IGQPGAKGEP GEFYFDLRLK 550 560 570 580 590 600 GDKGDPGFPG QPGMTGRAGS PGRDGHPGLP GPKGSPGSVG LKGERGPPGG VGFPGSRGDT 610 620 630 640 650 660 GPPGPPGYGP AGPIGDKGQA GFPGGPGSPG LPGPKGEPGK IVPLPGPPGA EGLPGSPGFP 670 680 690 700 710 720 GPQGDRGFPG TPGRPGLPGE KGAVGQPGIG FPGPPGPKGV DGLPGDMGPP GTPGRPGFNG 730 740 750 760 770 780 LPGNPGVQGQ KGEPGVGLPG LKGLPGLPGI PGTPGEKGSI GVPGVPGEHG AIGPPGLQGI 790 800 810 820 830 840 RGEPGPPGLP GSVGSPGVPG IGPPGARGPP GGQGPPGLSG PPGIKGEKGF PGFPGLDMPG 850 860 870 880 890 900 PKGDKGAQGL PGITGQSGLP GLPGQQGAPG IPGFPGSKGE MGVMGTPGQP GSPGPVGAPG 910 920 930 940 950 960 LPGEKGDHGF PGSSGPRGDP GLKGDKGDVG LPGKPGSMDK VDMGSMKGQK GDQGEKGQIG 970 980 990 1000 1010 1020 PIGEKGSRGD PGTPGVPGKD GQAGQPGQPG PKGDPGISGT PGAPGLPGPK GSVGGMGLPG 1030 1040 1050 1060 1070 1080 TPGEKGVPGI PGPQGSPGLP GDKGAKGEKG QAGPPGIGIP GLRGEKGDQG IAGFPGSPGE 1090 1100 1110 1120 1130 1140 KGEKGSIGIP GMPGSPGLKG SPGSVGYPGS PGLPGEKGDK GLPGLDGIPG VKGEAGLPGT 1150 1160 1170 1180 1190 1200 PGPTGPAGQK GEPGSDGIPG SAGEKGEPGL PGRGFPGFPG AKGDKGSKGE VGFPGLAGSP 1210 1220 1230 1240 1250 1260 GIPGSKGEQG FMGPPGPQGQ PGLPGSPGHA TEGPKGDRGP QGQPGLPGLP GPMGPPGLPG 1270 1280 1290 1300 1310 1320 IDGVKGDKGN PGWPGAPGVP GPKGDPGFQG MPGIGGSPGI TGSKGDMGPP GVPGFQGPKG 1330 1340 1350 1360 1370 1380 LPGLQGIKGD QGDQGVPGAK GLPGPPGPPG PYDIIKGEPG LPGPEGPPGL KGLQGLPGPK 1390 1400 1410 1420 1430 1440 GQQGVTGLVG IPGPPGIPGF DGAPGQKGEM GPAGPTGPRG FPGPPGPDGL PGSMGPPGTP 1450 1460 1470 1480 1490 1500 SVDHGFLVTR HSQTIDDPQC PSGTKILYHG YSLLYVQGNE RAHGQDLGTA GSCLRKFSTM 1510 1520 1530 1540 1550 1560 PFLFCNINNV CNFASRNDYS YWLSTPEPMP MSMAPITGEN IRPFISRCAV CEAPAMVMAV 1570 1580 1590 1600 1610 1620 HSQTIQIPPC PSGWSSLWIG YSFVMHTSAG AEGSGQALAS PGSCLEEFRS APFIECHGRG 1630 1640 1650 1660 TCNYYANAYS FWLATIERSE MFKKPTPSTL KAGELRTHVS RCQVCMRRT
	Isoform 2 [UniParc]. Checksum: E313ADCF65DA7BEC	FASTA	1,318	127,981
	10 20 30 40 50 60 MGPRLSVWLL LLPAALLLHE EHSRAAAKGG CAGSGCGKCD CHGVKGQKGE RGLPGLQGVI 70 80 90 100 110 120 GFPGMQGPEG PQGPPGQKGD TGEPGLPGTK GTRGPPGASG YPGNPGLPGI PGQDGPPGPP 130 140 150 160 170 180 GIPGCNGTKG ERGPLGPPGL PGFAGNPGPP GLPGMKGDPG EILGHVPGML LKGERGFPGI 190 200 210 220 230 240 PGTPGPPGLP GLQGPVGPPG FTGPPGPPGP PGPPGEKGQM GLSFQGPKGD KGDQGVSGPP 250 260 270 280 290 300 GVPGQAQVQE KGDFATKGEK GQKGEPGFQG MPGVGEKGEP GKPGPRGKPG KDGDKGEKGS 310 320 330 340 350 360 PGFPGEPGYP GLIGRQGPQG EKGEAGPPGP PGIVIGTGPL GEKGERGYPG TPGPRGEPGP 370 380 390 400 410 420 KGFPGLPGQP GPPGLPVPGQ AGAPGFPGER GEKGDRGFPG TSLPGPSGRD GLPGPPGSPG 430 440 450 460 470 480 PPGQPGYTNG IVECQPGPPG DQGPPGIPGQ PGFIGEIGEK GQKGESCLIC DIDGYRGPPG 490 500 510 520 530 540 PQGPPGEIGF PGQPGAKGLP GITGQSGLPG LPGQQGAPGI PGFPGSKGEM GVMGTPGQPG 550 560 570 580 590 600 SPGPVGAPGL PGEKGDHGFP GSSGPRGDPG LKGDKGDVGL PGKPGSMDKV DMGSMKGQKG 610 620 630 640 650 660 DQGEKGQIGP IGEKGSRGDP GTPGVPGKDG QAGQPGQPGP KGDPGISGTP GAPGLPGPKG 670 680 690 700 710 720 SVGGMGLPGT PGEKGVPGIP GPQGSPGLPG DKGAKGEKGQ AGPPGIGIPG LRGEKGDQGI 730 740 750 760 770 780 AGFPGSPGEK GEKGSIGIPG MPGSPGLKGS PGSVGYPGSP GLPGEKGDKG LPGLDGIPGV 790 800 810 820 830 840 KGEAGLPGTP GPTGPAGQKG EPGSDGIPGS AGEKGEPGLP GRGFPGFPGA KGDKGSKGEV 850 860 870 880 890 900 GFPGLAGSPG IPGSKGEQGF MGPPGPQGQP GLPGSPGHAT EGPKGDRGPQ GQPGLPGLPG 910 920 930 940 950 960 PMGPPGLPGI DGVKGDKGNP GWPGAPGVPG PKGDPGFQGM PGIGGSPGIT GSKGDMGPPG 970 980 990 1000 1010 1020 VPGFQGPKGL PGLQGIKGDQ GDQGVPGAKG LPGPPGPPGP YDIIKGEPGL PGPEGPPGLK 1030 1040 1050 1060 1070 1080 GLQGLPGPKG QQGVTGLVGI PGPPGIPGFD GAPGQKGEMG PAGPTGPRGF PGPPGPDGLP 1090 1100 1110 1120 1130 1140 GSMGPPGTPS VDHGFLVTRH SQTIDDPQCP SGTKILYHGY SLLYVQGNER AHGQDLGTAG 1150 1160 1170 1180 1190 1200 SCLRKFSTMP FLFCNINNVC NFASRNDYSY WLSTPEPMPM SMAPITGENI RPFISRCAVC 1210 1220 1230 1240 1250 1260 EAPAMVMAVH SQTIQIPPCP SGWSSLWIGY SFVMHTSAGA EGSGQALASP GSCLEEFRSA 1270 1280 1290 1300 1310 PFIECHGRGT CNYYANAYSF WLATIERSEM FKKPTPSTLK AGELRTHVSR CQVCMRRT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structural organization of the gene for the alpha 1 chain of human type IV collagen." Soininen R., Huotari M., Ganguly A., Prockop D.J., Tryggvason K. J. Biol. Chem. 264:13565-13571(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PRO-555.
[2]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] (ISOFORM 1), VARIANTS PRO-555 AND HIS-1334. Tissue: Brain.
[4]	"Completion of the amino acid sequence of the alpha 1 chain of human basement membrane collagen (type IV) reveals 21 non-triplet interruptions located within the collagenous domain." Brazel D., Oberbaeumer I., Dieringer H., Babel W., Glanville R.W., Deutzmann R., Kuehn K. Eur. J. Biochem. 168:529-536(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-943, VARIANT PRO-555. Tissue: Placenta.
[5]	"The structural genes for alpha 1 and alpha 2 chains of human type IV collagen are divergently encoded on opposite DNA strands and have an overlapping promoter region." Soininen R., Huotari M., Hostikka S.L., Prockop D.J., Tryggvason K. J. Biol. Chem. 263:17217-17220(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28.
[6]	"Amino acid sequence of the N-terminal aggregation and cross-linking region (7S domain) of the alpha 1 (IV) chain of human basement membrane collagen." Glanville R.W., Qian R.Q., Siebold B., Risteli J., Kuehn K. Eur. J. Biochem. 152:213-219(1985) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-243.
[7]	"Complete primary structure of the alpha 1-chain of human basement membrane (type IV) collagen." Soininen R., Haka-Risku T., Prockop D.J., Tryggvason K. FEBS Lett. 225:188-194(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 46-1257, VARIANT PRO-555. Tissue: Placenta.
[8]	"Structure of human-basement-membrane (type IV) collagen. Complete amino-acid sequence of a 914-residue-long pepsin fragment from the alpha 1(IV) chain." Babel W., Glanville R.W. Eur. J. Biochem. 143:545-556(1984) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 534-1447.
[9]	"cDNA clones coding for the pro-alpha1(IV) chain of human type IV procollagen reveal an unusual homology of amino acid sequences in two halves of the carboxyl-terminal domain." Pihlajaniemi T., Tryggvason K., Myers J.C., Kurkinen M., Lebo R., Cheung M.-C., Prockop D.J., Boyd C.D. J. Biol. Chem. 260:7681-7687(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1256-1669.
[10]	"Restricted homology between human alpha 1 type IV and other procollagen chains." Brinker J.M., Gudas L.J., Loidl H.R., Wang S.-Y., Rosenbloom J., Kefalides N.A., Myers J.C. Proc. Natl. Acad. Sci. U.S.A. 82:3649-3653(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1259-1669.
[11]	"The arrangement of intra- and intermolecular disulfide bonds in the carboxyterminal, non-collagenous aggregation and cross-linking domain of basement-membrane type IV collagen." Siebold B., Deutzmann R., Kuehn K. Eur. J. Biochem. 176:617-624(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 1441-1669, DISULFIDE BONDS. Tissue: Placenta.
[12]	"Anti-angiogenic cues from vascular basement membrane collagen." Colorado P.C., Torre A., Kamphaus G., Maeshima Y., Hopfer H., Takahashi K., Volk R., Zamborsky E.D., Herman S., Sarkar P.K., Ericksen M.B., Dhanabal M., Simons M., Post M., Kufe D.W., Weichselbaum R.R., Sukhatme V.P., Kalluri R. Cancer Res. 60:2520-2526(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1441-1669, FUNCTION OF ARRESTEN, TISSUE SPECIFICITY.
[13]	"Arresten, a collagen-derived inhibitor of angiogenesis." Fu J., Bai X., Wang W., Ruan C. Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1441-1669.
[14]	Peng X., Yin B., Yuan J., Qiang B. Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1441-1669.
[15]	"Molecular cloning and sequencing of human arresten gene." Zheng Q.C., Song Z.F., Zheng Y.W., Li Y.Q., Shu X. Zhonghua Shi Yan Wai Ke Za Zhi 19:46-47(2002) Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1441-1669.
[16]	"Cloning and expression of arresten in Escherichia coli and Pachia pastoris." He A.B. Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1441-1669.
[17]	"Construction of recombinant plasmid and prokaryotic expression in E. coli and biological activity analysis of human placenta arresten gene." Zheng J.P., Tang H.Y., Chen X.J., Yu B.F., Xie J., Wu T.C. Hepatobiliary Pancreat. Dis. Int. 5:74-79(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1441-1669, FUNCTION, TISSUE SPECIFICITY. Tissue: Placenta.
[18]	"Human alpha1 type IV collagen NC1 domain exhibits distinct antiangiogenic activity mediated by alpha1beta1 integrin." Sudhakar A., Nyberg P., Keshamouni V.G., Mannam A.P., Li J., Sugimoto H., Cosgrove D., Kalluri R. J. Clin. Invest. 115:2801-2810(2005) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF RECEPTOR, FUNCTION OF ARRESTEN.
[19]	"Characterization of the anti-angiogenic properties of arresten, an alpha1beta1 integrin-dependent collagen-derived tumor suppressor." Nyberg P., Xie L., Sugimoto H., Colorado P., Sund M., Holthaus K., Sudhakar A., Salo T., Kalluri R. Exp. Cell Res. 314:3292-3305(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF RECEPTOR, FUNCTION OF ARRESTEN.
[20]	"The 1.9-A crystal structure of the noncollagenous (NC1) domain of human placenta collagen IV shows stabilization via a novel type of covalent Met-Lys cross-link." Than M.E., Henrich S., Huber R., Ries A., Mann K., Kuhn K., Timpl R., Bourenkov G.P., Bartunik H.D., Bode W. Proc. Natl. Acad. Sci. U.S.A. 99:6607-6612(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1441-1669, ADDITIONAL INTERCHAIN LINKS.
[21]	"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: VARIANTS POREN1 SER-749 AND ARG-1236.
[22]	"Novel mutations in three families confirm a major role of COL4A1 in hereditary porencephaly." Breedveld G., de Coo I.F., Lequin M.H., Arts W.F.M., Heutink P., Gould D.B., John S.W.M., Oostra B., Mancini G.M.S. J. Med. Genet. 43:490-495(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS POREN1 ASP-1130 AND ARG-1423.
[23]	"Role of COL4A1 in small-vessel disease and hemorrhagic stroke." Gould D.B., Phalan F.C., van Mil S.E., Sundberg J.P., Vahedi K., Massin P., Bousser M.G., Heutink P., Miner J.H., Tournier-Lasserve E., John S.W.M. N. Engl. J. Med. 354:1489-1496(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BSVDH GLU-562.
[24]	"COL4A1 mutation in Axenfeld-Rieger anomaly with leukoencephalopathy and stroke." Sibon I., Coupry I., Menegon P., Bouchet J.P., Gorry P., Burgelin I., Calvas P., Orignac I., Dousset V., Lacombe D., Orgogozo J.M., Arveiler B., Goizet C. Ann. Neurol. 62:177-184(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BSVDH ASP-720.
[25]	"COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps." Plaisier E., Gribouval O., Alamowitch S., Mougenot B., Prost C., Verpont M.C., Marro B., Desmettre T., Cohen S.Y., Roullet E., Dracon M., Fardeau M., Van Agtmael T., Kerjaschki D., Antignac C., Ronco P. N. Engl. J. Med. 357:2687-2695(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HANAC VAL-498; ARG-519 AND GLU-528.
[26]	"A sulfilimine bond identified in collagen IV." Vanacore R., Ham A.-J.L., Voehler M., Sanders C.R., Conrads T.P., Veenstra T.D., Sharpless K.B., Dawson P.E., Hudson B.G. Science 325:1230-1234(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERCHAIN SULFILIMINE BONDS.
[27]	"COL4A1 mutation in a patient with sporadic, recurrent intracerebral hemorrhage." Vahedi K., Kubis N., Boukobza M., Arnoult M., Massin P., Tournier-Lasserve E., Bousser M.G. Stroke 38:1461-1464(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BSVDH ARG-805.
[28]	"COL4A1 mutation in two preterm siblings with antenatal onset of parenchymal hemorrhage." de Vries L.S., Koopman C., Groenendaal F., Van Schooneveld M., Verheijen F.W., Verbeek E., Witkamp T.D., van der Worp H.B., Mancini G. Ann. Neurol. 65:12-18(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT POREN1 ARG-1580.
[29]	"Novel COL4A1 mutations associated with HANAC syndrome: a role for the triple helical CB3[IV] domain." Plaisier E., Chen Z., Gekeler F., Benhassine S., Dahan K., Marro B., Alamowitch S., Paques M., Ronco P. Am. J. Med. Genet. A 152:2550-2555(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HANAC ARG-498; ARG-510 AND LEU-525.
[30]	"Ophthalmological features associated with COL4A1 mutations." Coupry I., Sibon I., Mortemousque B., Rouanet F., Mine M., Goizet C. Arch. Ophthalmol. 128:483-489(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BSVDH ASP-720 AND ARG-755.
[31]	"A dominantly inherited mutation in collagen IV A1 (COL4A1) causing childhood onset stroke without porencephaly." Shah S., Kumar Y., McLean B., Churchill A., Stoodley N., Rankin J., Rizzu P., van der Knaap M., Jardine P. Eur. J. Paediatr. Neurol. 14:182-187(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BSVDH ARG-755.
[32]	"Sequence variants in COL4A1 and COL4A2 genes in Ecuadorian families with keratoconus." Karolak J.A., Kulinska K., Nowak D.M., Pitarque J.A., Molinari A., Rydzanicz M., Bejjani B.A., Gajecka M. Mol. Vis. 17:827-843(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LEU-7; PRO-555 AND HIS-1334.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M26576 , J04217, M26550, M26540, M26542, M26543, M26544, M26545, M26546, M26547, M26537, M26538, M26548, M26549, M26551, M26552, M26553, M26554, M26555, M26556, M26557, M26539, M26558, M26559, M26560, M26561, M26562, M26536, M26563, M26541, M26564, M26565, M26566, M26567, M26568, M26569, M26570, M26571, M26572, M26573, M26574, M26575 Genomic DNA. Translation: AAA53098.1.
AL161773, AL390755 Genomic DNA. Translation: CAH71365.1.
AL390755, AL161773 Genomic DNA. Translation: CAH74130.1.
AL161773, AL390755 Genomic DNA. Translation: CAM14222.1.
AL390755, AL161773 Genomic DNA. Translation: CAM20295.1.
BC047305 mRNA. Translation: AAH47305.1.
BC151220 mRNA. Translation: AAI51221.1.
X05561 mRNA. Translation: CAA29075.1.
Y00706 mRNA. Translation: CAA68698.1.
M10940 mRNA. Translation: AAA52006.1.
M11315 mRNA. Translation: AAA52042.1.
AF258349 mRNA. Translation: AAF72630.1.
AF363672 mRNA. Translation: AAK53382.1.
AF400431 mRNA. Translation: AAK92480.1.
AY285780 mRNA. Translation: AAP43112.1.
AF536207 mRNA. Translation: AAM97359.1.
DQ464183 mRNA. Translation: ABE73157.1.

IPI

IPI00743696.
IPI00873684.

PIR

CGHU4B. S16876.

RefSeq

NP_001836.2. NM_001845.4.

UniGene

Hs.17441.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LI1	X-ray	1.90	A/B/D/E	1441-1669	[»]

ProteinModelPortal

P02462.

ModBase

Search...

Protein-protein interaction databases

IntAct

P02462. 22 interactions.

MINT

MINT-6743187.

STRING

9606.ENSP00000364979.

PTM databases

PhosphoSite

P02462.

Polymorphism databases

DMDM

125987809.

Proteomic databases

PaxDb

P02462.

PRIDE

P02462.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000375820; ENSP00000364979; ENSG00000187498.
ENST00000397198; ENSP00000380382; ENSG00000187498.

GeneID

1282.

KEGG

hsa:1282.

UCSC

uc001vqw.4. human.

Organism-specific databases

CTD

1282.

GeneCards

GC13M110801.

HGNC

HGNC:2202. COL4A1.

HPA

CAB001695.

MIM

120130. gene.
175780. phenotype.
607595. phenotype.
611773. phenotype.

neXtProt

NX_P02462.

Orphanet

73229. Autosomal dominant familial hematuria - retinal arteriolar tortuosity - contractures.
99810. Familial porencephaly.
36383. Familial vascular leukoencephalopathy.
899. Walker-Warburg syndrome.

PharmGKB

PA26717.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG12793.

HOVERGEN

HBG004933.

KO

K06237.

OMA

VAHGFLV.

OrthoDB

EOG45DWPF.

PhylomeDB

P02462.

Enzyme and pathway databases

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_118779. Extracellular matrix organization.

Gene expression databases

ArrayExpress

P02462.

Bgee

P02462.

CleanEx

HS_COL4A1.

Genevestigator

P02462.

GermOnline

ENSG00000187498. Homo sapiens.

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. 21 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

COL4A1. human.

EvolutionaryTrace

P02462.

GenomeRNAi

1282.

NextBio

5181.

SOURCE

Search...

Entry information

Entry name

CO4A1_HUMAN

Accession

Primary (citable) accession number: P02462
Secondary accession number(s): A7E2W4 , B1AM70, Q1P9S9, Q5VWF6, Q86X41, Q8NF88, Q9NYC5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	February 6, 2007
Last modified:	May 29, 2013
This is version 152 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.