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Q01955 (CO4A3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 169. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Collagen alpha-3(IV) chain
Alternative name(s):
Goodpasture antigen

Cleaved into the following chain:

  1. Tumstatin
Gene names
Name:COL4A3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1670 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.10 Ref.17 Ref.20 Ref.21

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.10 Ref.17 Ref.20 Ref.21

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. Associates with LAMB2 at the neuromuscular junction and in GBM By similarity. Ref.16 Ref.19 Ref.20

Subcellular location

Secretedextracellular spaceextracellular matrixbasement membrane. Note: Colocalizes with COL4A4 and COL4A5 in GBM, tubular basement membrane (TBM) and synaptic basal lamina (BL) By similarity.

Tissue specificity

Alpha 3 and alpha 4 type IV collagens are colocalized and present in kidney, eye, basement membranes of lens capsule, cochlea, lung, skeletal muscle, aorta, synaptic fibers, fetal kidney and fetal lung. Ref.1 reports similar levels of expression of alpha 3 and alpha 4 type IV collagens in kidney, but Ref.15 reports that in kidney levels of alpha 3 type IV collagen are significantly lower than those of alpha 4 type IV collagen. According to Ref.1, alpha 3 type IV collagen is not detected in heart, brain, placenta, liver, pancreas, extrasynaptic muscle fibers, endoneurial and perineurial nerves, fetal brain, fetal heart and fetal liver. According to Ref.15, alpha 3 type IV collagen is strongly expressed in pancreas, neuroretina and calvaria and not expressed in adrenal, ileum and skin. Isoform 1 and isoform 3 are strongly expressed in kidney, lung, suprarenal capsule, muscle and spleen, in each of these tissues isoform 1 is more abundant than isoform 3. Isoform 1 and isoform 3 are expressed at low levels in artery, fat, pericardium and peripherical nerve, but not in placenta, mesangium, skin, pleura and cultured umbilical endothelial cells. Ref.1 Ref.14 Ref.15

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.

Isoform 2 contains an additional N-linked glycosylation site.

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 By similarity.

Phosphorylated by the Goodpasture antigen-binding protein/COL4A3BP. Ref.16

Involvement in disease

Autoantibodies against the NC1 domain of alpha 3(IV) are found in Goodpasture syndrome, an autoimmune disease of lung and kidney.

Alport syndrome, autosomal recessive (APSAR) [MIM:203780]: A syndrome characterized by progressive glomerulonephritis, glomerular basement membrane defects, renal failure, sensorineural deafness and specific eye abnormalities (lenticonous and macular flecks). The disorder shows considerable heterogeneity in that families differ in the age of end-stage renal disease and the occurrence of deafness.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3 Ref.25

Hematuria, benign familial (BFH) [MIM:141200]: An autosomal dominant condition characterized by non-progressive isolated microscopic hematuria that does not result in renal failure. It is characterized pathologically by thinning of the glomerular basement membrane.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.24

Alport syndrome, autosomal dominant (APSAD) [MIM:104200]: A syndrome characterized by progressive glomerulonephritis, glomerular basement membrane defects, renal failure, sensorineural deafness and specific eye abnormalities (lenticonous and macular flecks). The disorder shows considerable heterogeneity in that families differ in the age of end-stage renal disease and the occurrence of deafness.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3 Ref.18

Miscellaneous

The epitopes recognized by the Goodpasture autoantibodies are sequestered within the NC1 hexamer of the type IV collagen network.

Sequence similarities

Belongs to the type IV collagen family.

Contains 1 collagen IV NC1 (C-terminal non-collagenous) domain.

Ontologies

Keywords
   Biological processCell adhesion
   Cellular componentBasement membrane
Extracellular matrix
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseAlport syndrome
Deafness
Disease mutation
   DomainCollagen
Repeat
Signal
   PTMDisulfide bond
Glycoprotein
Hydroxylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay Ref.10. Source: UniProtKB

axon guidance

Traceable author statement. Source: Reactome

blood circulation

Traceable author statement Ref.10. Source: ProtInc

cell adhesion

Inferred from electronic annotation. Source: UniProtKB-KW

cell proliferation

Inferred from direct assay Ref.10. Source: UniProtKB

cell surface receptor signaling pathway

Non-traceable author statement Ref.10. Source: UniProtKB

collagen catabolic process

Traceable author statement. Source: Reactome

endothelial cell apoptotic process

Inferred from direct assay Ref.10. Source: UniProtKB

extracellular matrix disassembly

Traceable author statement. Source: Reactome

extracellular matrix organization

Traceable author statement. Source: Reactome

glomerular basement membrane development

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of angiogenesis

Inferred from direct assay Ref.10Ref.20. Source: UniProtKB

negative regulation of cell proliferation

Traceable author statement Ref.17. Source: ProtInc

negative regulation of endopeptidase activity

Non-traceable author statement Ref.10. Source: GOC

response to glucose

Inferred from electronic annotation. Source: Ensembl

sensory perception of sound

Traceable author statement PubMed 7987396. Source: ProtInc

   Cellular_componentbasement membrane

Inferred from direct assay Ref.10. Source: UniProtKB

collagen type IV trimer

Inferred from direct assay Ref.10. Source: UniProtKB

endoplasmic reticulum lumen

Traceable author statement. Source: Reactome

extracellular region

Traceable author statement. Source: Reactome

   Molecular_functionextracellular matrix structural constituent

Inferred from electronic annotation. Source: InterPro

integrin binding

Inferred from direct assay Ref.20. Source: UniProtKB

metalloendopeptidase inhibitor activity

Non-traceable author statement Ref.10. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.16Ref.20. Source: UniProtKB

structural molecule activity

Non-traceable author statement PubMed 3025878. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Note: The majority of isoforms differ in the C-terminal part of the NC1 domain.
Isoform 1 (identifier: Q01955-1)

Also known as: GP;

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: Q01955-2)

Also known as: V; GP-V;

The sequence of this isoform differs from the canonical sequence as follows:
     1586-1670: FTSAGSEGTG...RCQVCMKKRH → KAYSINCESW...NKVMTEHAVI
Isoform 3 (identifier: Q01955-3)

Also known as: L5; GP-III; GP-III/V;

The sequence of this isoform differs from the canonical sequence as follows:
     1488-1670: GTLGSCLQRF...RCQVCMKKRH → DALFVKVLRSP
Isoform 4 (identifier: Q01955-4)

Also known as: GP-III/IV/V;

The sequence of this isoform differs from the canonical sequence as follows:
     1488-1670: GTLGSCLQRF...RCQVCMKKRH → ESLFHQL
Isoform 5 (identifier: Q01955-5)

Also known as: GP-II/III/IV/V;

The sequence of this isoform differs from the canonical sequence as follows:
     1418-1424: GPAGSDG → ESLFHQL
     1425-1670: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2828 Potential
Chain29 – 16701642Collagen alpha-3(IV) chain
PRO_0000005844
Chain1426 – 1670245Tumstatin
PRO_0000279684

Regions

Domain1445 – 1669225Collagen IV NC1
Region29 – 42147S domain
Region43 – 14381396Triple-helical region
Region1427 – 144418Epitope recognized by Goodpasture antibodies
Region1479 – 155779Required for the anti-angiogenic activity of tumstatin
Region1610 – 162819Required for the anti-tumor cell activity of tumstatin
Motif791 – 7933Cell attachment site Potential
Motif996 – 9983Cell attachment site Potential
Motif1154 – 11563Cell attachment site Potential
Motif1306 – 13083Cell attachment site Potential
Motif1345 – 13473Cell attachment site Potential
Motif1432 – 14343Cell attachment site Potential

Sites

Site1426 – 14272Cleavage; by collagenase By similarity

Amino acid modifications

Glycosylation2531N-linked (GlcNAc...) Potential
Disulfide bond1460 ↔ 1551Or C-1460 with C-1548 By similarity
Disulfide bond1493 ↔ 1548Or C-1493 with C-1551 By similarity
Disulfide bond1505 ↔ 1511 By similarity
Disulfide bond1570 ↔ 1665Or C-1570 with C-1662 By similarity
Disulfide bond1604 ↔ 1662Or C-1604 with C-1665 By similarity
Disulfide bond1616 ↔ 1622 By similarity
Cross-link1414Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.22
Cross-link1533S-Lysyl-methionine sulfilimine (Met-Lys) (interchain with K-1651) By similarity
Cross-link1651S-Lysyl-methionine sulfilimine (Lys-Met) (interchain with M-1533) By similarity

Natural variations

Alternative sequence1418 – 14247GPAGSDG → ESLFHQL in isoform 5.
VSP_023498
Alternative sequence1425 – 1670246Missing in isoform 5.
VSP_023499
Alternative sequence1488 – 1670183GTLGS…MKKRH → DALFVKVLRSP in isoform 3.
VSP_001171
Alternative sequence1488 – 1670183GTLGS…MKKRH → ESLFHQL in isoform 4.
VSP_023500
Alternative sequence1586 – 167085FTSAG…MKKRH → KAYSINCESWGIRKNNKSLS GVHEEKTLKLKKTAELVFFI LKNKVMTEHAVI in isoform 2.
VSP_001170
Natural variant431G → R. Ref.3
Corresponds to variant rs13424243 [ dbSNP | Ensembl ].
VAR_011202
Natural variant1411L → P. Ref.1 Ref.3
Corresponds to variant rs10178458 [ dbSNP | Ensembl ].
VAR_030944
Natural variant1621E → G. Ref.1
Corresponds to variant rs6436669 [ dbSNP | Ensembl ].
VAR_011203
Natural variant2971G → E in APSAR. Ref.3
VAR_011204
Natural variant3261D → Y. Ref.3
Corresponds to variant rs55703767 [ dbSNP | Ensembl ].
VAR_011205
Natural variant4071G → R in APSAR. Ref.3
VAR_011206
Natural variant4081R → H. Ref.3
Corresponds to variant rs34505188 [ dbSNP | Ensembl ].
VAR_011207
Natural variant4511H → R. Ref.3
Corresponds to variant rs11677877 [ dbSNP | Ensembl ].
VAR_011208
Natural variant5321G → D in APSAR. Ref.25
VAR_030945
Natural variant5741P → L. Ref.1
Corresponds to variant rs28381984 [ dbSNP | Ensembl ].
VAR_011209
Natural variant6401G → R in APSAR. Ref.3
VAR_011210
Natural variant7391G → R in APSAR. Ref.25
VAR_030946
Natural variant8341K → R.
Corresponds to variant rs56226424 [ dbSNP | Ensembl ].
VAR_061118
Natural variant8531G → R in APSAR. Ref.25
VAR_030947
Natural variant9851G → V in BFH. Ref.24
VAR_030948
Natural variant10151G → E in BFH. Ref.24
VAR_030949
Natural variant11671G → R in APSAD; in isolated microhematuria at heterozygosity. Ref.3
VAR_011211
Natural variant12071G → E in APSAR; in isolated microhematuria at heterozygosity. Ref.3
VAR_011212
Natural variant12151R → Q in APSAR; unknown pathological significance. Ref.3
VAR_011213
Natural variant12161G → R in APSAR. Ref.25
VAR_030950
Natural variant12691D → E. Ref.3
Corresponds to variant rs57611801 [ dbSNP | Ensembl ].
VAR_011214
Natural variant12771G → S in APSAR. Ref.3
Corresponds to variant rs190598500 [ dbSNP | Ensembl ].
VAR_011215
Natural variant13301I → T in APSAR; unknown pathological significance. Ref.3
VAR_011216
Natural variant13341G → E in APSAR. Ref.3
VAR_011217
Natural variant13471D → E in APSAR; unknown pathological significance. Ref.3
Corresponds to variant rs73996414 [ dbSNP | Ensembl ].
VAR_011218
Natural variant14741L → P. Ref.3 Ref.23
Corresponds to variant rs200302125 [ dbSNP | Ensembl ].
VAR_001908
Natural variant14951Q → R.
Corresponds to variant rs77964815 [ dbSNP | Ensembl ].
VAR_001909
Natural variant16611R → C in APSAR. Ref.3
VAR_011219

Experimental info

Sequence conflict9111T → R in CAC36101. Ref.3
Sequence conflict15391R → I in AAA18942. Ref.11
Sequence conflict15941T → A in AAB19637. Ref.12
Sequence conflict1663 – 16642QV → HL in AAA52044. Ref.13
Isoform 2:
Sequence conflict15391R → I in AAA18942. Ref.11

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (GP) [UniParc].

Last modified March 6, 2007. Version 3.
Checksum: AA65D50903D82B99

FASTA1,670161,813
        10         20         30         40         50         60 
MSARTAPRPQ VLLLPLLLVL LAAAPAASKG CVCKDKGQCF CDGAKGEKGE KGFPGPPGSP 

        70         80         90        100        110        120 
GQKGFTGPEG LPGPQGPKGF PGLPGLTGSK GVRGISGLPG FSGSPGLPGT PGNTGPYGLV 

       130        140        150        160        170        180 
GVPGCSGSKG EQGFPGLPGT LGYPGIPGAA GLKGQKGAPA KEEDIELDAK GDPGLPGAPG 

       190        200        210        220        230        240 
PQGLPGPPGF PGPVGPPGPP GFFGFPGAMG PRGPKGHMGE RVIGHKGERG VKGLTGPPGP 

       250        260        270        280        290        300 
PGTVIVTLTG PDNRTDLKGE KGDKGAMGEP GPPGPSGLPG ESYGSEKGAP GDPGLQGKPG 

       310        320        330        340        350        360 
KDGVPGFPGS EGVKGNRGFP GLMGEDGIKG QKGDIGPPGF RGPTEYYDTY QEKGDEGTPG 

       370        380        390        400        410        420 
PPGPRGARGP QGPSGPPGVP GSPGSSRPGL RGAPGWPGLK GSKGERGRPG KDAMGTPGSP 

       430        440        450        460        470        480 
GCAGSPGLPG SPGPPGPPGD IVFRKGPPGD HGLPGYLGSP GIPGVDGPKG EPGLLCTQCP 

       490        500        510        520        530        540 
YIPGPPGLPG LPGLHGVKGI PGRQGAAGLK GSPGSPGNTG LPGFPGFPGA QGDPGLKGEK 

       550        560        570        580        590        600 
GETLQPEGQV GVPGDPGLRG QPGRKGLDGI PGTPGVKGLP GPKGELALSG EKGDQGPPGD 

       610        620        630        640        650        660 
PGSPGSPGPA GPAGPPGYGP QGEPGLQGTQ GVPGAPGPPG EAGPRGELSV STPVPGPPGP 

       670        680        690        700        710        720 
PGPPGHPGPQ GPPGIPGSLG KCGDPGLPGP DGEPGIPGIG FPGPPGPKGD QGFPGTKGSL 

       730        740        750        760        770        780 
GCPGKMGEPG LPGKPGLPGA KGEPAVAMPG GPGTPGFPGE RGNSGEHGEI GLPGLPGLPG 

       790        800        810        820        830        840 
TPGNEGLDGP RGDPGQPGPP GEQGPPGRCI EGPRGAQGLP GLNGLKGQQG RRGKTGPKGD 

       850        860        870        880        890        900 
PGIPGLDRSG FPGETGSPGI PGHQGEMGPL GQRGYPGNPG ILGPPGEDGV IGMMGFPGAI 

       910        920        930        940        950        960 
GPPGPPGNPG TPGQRGSPGI PGVKGQRGTP GAKGEQGDKG NPGPSEISHV IGDKGEPGLK 

       970        980        990       1000       1010       1020 
GFAGNPGEKG NRGVPGMPGL KGLKGLPGPA GPPGPRGDLG STGNPGEPGL RGIPGSMGNM 

      1030       1040       1050       1060       1070       1080 
GMPGSKGKRG TLGFPGRAGR PGLPGIHGLQ GDKGEPGYSE GTRPGPPGPT GDPGLPGDMG 

      1090       1100       1110       1120       1130       1140 
KKGEMGQPGP PGHLGPAGPE GAPGSPGSPG LPGKPGPHGD LGFKGIKGLL GPPGIRGPPG 

      1150       1160       1170       1180       1190       1200 
LPGFPGSPGP MGIRGDQGRD GIPGPAGEKG ETGLLRAPPG PRGNPGAQGA KGDRGAPGFP 

      1210       1220       1230       1240       1250       1260 
GLPGRKGAMG DAGPRGPTGI EGFPGPPGLP GAIIPGQTGN RGPPGSRGSP GAPGPPGPPG 

      1270       1280       1290       1300       1310       1320 
SHVIGIKGDK GSMGHPGPKG PPGTAGDMGP PGRLGAPGTP GLPGPRGDPG FQGFPGVKGE 

      1330       1340       1350       1360       1370       1380 
KGNPGFLGSI GPPGPIGPKG PPGVRGDPGT LKIISLPGSP GPPGTPGEPG MQGEPGPPGP 

      1390       1400       1410       1420       1430       1440 
PGNLGPCGPR GKPGKDGKPG TPGPAGEKGN KGSKGEPGPA GSDGLPGLKG KRGDSGSPAT 

      1450       1460       1470       1480       1490       1500 
WTTRGFVFTR HSQTTAIPSC PEGTVPLYSG FSFLFVQGNQ RAHGQDLGTL GSCLQRFTTM 

      1510       1520       1530       1540       1550       1560 
PFLFCNVNDV CNFASRNDYS YWLSTPALMP MNMAPITGRA LEPYISRCTV CEGPAIAIAV 

      1570       1580       1590       1600       1610       1620 
HSQTTDIPPC PHGWISLWKG FSFIMFTSAG SEGTGQALAS PGSCLEEFRA SPFLECHGRG 

      1630       1640       1650       1660       1670 
TCNYYSNSYS FWLASLNPER MFRKPIPSTV KAGELEKIIS RCQVCMKKRH 

« Hide

Isoform 2 (V) (GP-V) [UniParc].

Checksum: 92396B115CEA21DF
Show »

FASTA1,637158,336
Isoform 3 (L5) (GP-III) (GP-III/V) [UniParc].

Checksum: 74CF6C2B17B98686
Show »

FASTA1,498142,741
Isoform 4 (GP-III/IV/V) [UniParc].

Checksum: C24C75A6029B73C8
Show »

FASTA1,494142,369
Isoform 5 (GP-II/III/IV/V) [UniParc].

Checksum: 80BA77353C7013C6
Show »

FASTA1,424135,079

References

« Hide 'large scale' references
[1]"Complete primary structure of the human alpha 3(IV) collagen chain. Coexpression of the alpha 3(IV) and alpha 4(IV) collagen chains in human tissues."
Mariyama M., Leinonen A., Mochizuki T., Tryggvason K., Reeders S.T.
J. Biol. Chem. 269:23013-23017(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANTS PRO-141; GLY-162 AND LEU-574.
Tissue: Kidney.
[2]Leinonen A.
Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[3]"Structure of the human type IV collagen gene COL4A3 and mutations in autosomal Alport syndrome."
Heidet L., Arrondel C., Forestier L., Cohen-Solal L., Mollet G., Gutierrez B., Stavrou C., Gubler M.-C., Antignac C.
J. Am. Soc. Nephrol. 12:97-106(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), VARIANTS APSAR GLU-297; ARG-407; ARG-640; GLU-1207; GLN-1215; SER-1277; THR-1330; GLU-1334; GLU-1347 AND CYS-1661, VARIANT APSAD ARG-1167, VARIANTS ARG-43; PRO-141; TYR-326; HIS-408; ARG-451; GLU-1269 AND PRO-1474.
[4]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Two genes, COL4A3 and COL4A4 coding for the human alpha3(IV) and alpha4(IV) collagen chains are arranged head-to-head on chromosome 2q36."
Momota R., Sugimoto M., Oohashi T., Kigasawa K., Yoshioka H., Ninomiya Y.
FEBS Lett. 424:11-16(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-29.
[6]"Molecular cloning of the human Goodpasture antigen demonstrates it to be the alpha 3 chain of type IV collagen."
Turner N., Mason P.J., Brown R., Fox M., Povey S., Rees A., Pusey C.D.
J. Clin. Invest. 89:592-601(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1331-1670 (ISOFORM 1).
Tissue: Kidney.
[7]"Exon/intron structure of the human alpha 3(IV) gene encompassing the Goodpasture antigen (alpha 3(IV)NC1). Identification of a potentially antigenic region at the triple helix/NC1 domain junction."
Quinones S., Bernal D., Garcia-Sogo M., Elena S.F., Saus J.
J. Biol. Chem. 267:19780-19784(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1386-1670 (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
[8]Erratum
Quinones S., Bernal D., Garcia-Sogo M., Elena S.F., Saus J.
J. Biol. Chem. 269:17358-17358(1994) [PubMed] [Europe PMC] [Abstract]
[9]"Characterization and expression of multiple alternatively spliced transcripts of the Goodpasture antigen gene region. Goodpasture antibodies recognize recombinant proteins representing the autoantigen and one of its alternative forms."
Penades J.R., Bernal D., Revert F., Johansson C., Fresquet V.J., Cervera J., Wieslander J., Quinones S., Saus J.
Eur. J. Biochem. 229:754-760(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1386-1670 (ISOFORMS 1; 2; 3; 4 AND 5), ALTERNATIVE SPLICING.
Tissue: Kidney.
[10]"Distinct antitumor properties of a type IV collagen domain derived from basement membrane."
Maeshima Y., Colorado P.C., Torre A., Holthaus K.A., Grunkemeyer J.A., Ericksen M.B., Hopfer H., Xiao Y., Stillman I.E., Kalluri R.
J. Biol. Chem. 275:21340-21348(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1426-1670 (ISOFORM 1), FUNCTION.
[11]"Alternative splicing of the NC1 domain of the human alpha 3(IV) collagen gene. Differential expression of mRNA transcripts that predict three protein variants with distinct carboxyl regions."
Feng L., Xia Y., Wilson C.B.
J. Biol. Chem. 269:2342-2348(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1439-1670 (ISOFORMS 2 AND 3), ALTERNATIVE SPLICING (ISOFORM 1).
Tissue: Kidney.
[12]"Sequence and localization of a partial cDNA encoding the human alpha 3 chain of type IV collagen."
Morrison K.E., Mariyama M., Yang-Feng T.L., Reeders S.T.
Am. J. Hum. Genet. 49:545-554(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1453-1670 (ISOFORM 1).
[13]Ding J.
Submitted (JAN-1993) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1644-1670 (ISOFORM 1).
Tissue: Kidney.
[14]"The human mRNA encoding the Goodpasture antigen is alternatively spliced."
Bernal D., Quinones S., Saus J.
J. Biol. Chem. 268:12090-12094(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
Tissue: Kidney.
[15]"Complete primary structure of the human type IV collagen alpha 4(IV) chain. Comparison with structure and expression of the other alpha (IV) chains."
Leinonen A., Mariyama M., Mochizuki T., Tryggvason K., Reeders S.T.
J. Biol. Chem. 269:26172-26177(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[16]"Characterization of a novel type of serine/threonine kinase that specifically phosphorylates the human goodpasture antigen."
Raya A., Revert F., Navarro S., Saus J.
J. Biol. Chem. 274:12642-12649(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH COL4A3BP, PHOSPHORYLATION.
[17]"Two RGD-independent alpha vbeta 3 integrin binding sites on tumstatin regulate distinct anti-tumor properties."
Maeshima Y., Colorado P.C., Kalluri R.
J. Biol. Chem. 275:23745-23750(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[18]"Autosomal dominant Alport syndrome caused by a COL4A3 splice site mutation."
van der Loop F.T.L., Heidet L., Timmer E.D.J., van den Bosch B.J.C., Leinonen A., Antignac C., Jefferson J.A., Maxwell A.P., Monnens L.A.H., Schroder C.H., Smeets H.J.M.
Kidney Int. 58:1870-1875(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN APSAD.
[19]"Quaternary organization of the goodpasture autoantigen, the alpha 3(IV) collagen chain. Sequestration of two cryptic autoepitopes by intrapromoter interactions with the alpha4 and alpha5 NC1 domains."
Borza D.B., Bondar O., Todd P., Sundaramoorthy M., Sado Y., Ninomiya Y., Hudson B.G.
J. Biol. Chem. 277:40075-40083(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: HEXAMERIZATION.
[20]"Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by alpha v beta 3 and alpha 5 beta 1 integrins."
Sudhakar A., Sugimoto H., Yang C., Lively J., Zeisberg M., Kalluri R.
Proc. Natl. Acad. Sci. U.S.A. 100:4766-4771(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ITGB3.
[21]"Implication of tumstatin in tumor progression of human bronchopulmonary carcinomas."
Caudroy S., Cucherousset J., Lorenzato M., Zahm J.-M., Martinella-Catusse C., Polette M., Birembaut P.
Hum. Pathol. 35:1218-1222(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[22]"Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry."
Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D.
Proteomics 7:868-874(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-1414.
Tissue: Mammary cancer.
[23]"Mutations in the type IV collagen alpha 3 (COL4A3) gene in autosomal recessive Alport syndrome."
Lemmink H.H., Mochizuki T., van den Heuvel L.P.W.J., Schroeder C.H., Barrientos A., Monnens L.A.H., van Oost B.A., Brunner H.G., Reeders S.T., Smeets H.J.M.
Hum. Mol. Genet. 3:1269-1273(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PRO-1474.
[24]"Mutations in the COL4A4 and COL4A3 genes cause familial benign hematuria."
Badenas C., Praga M., Tazon B., Heidet L., Arrondel C., Armengol A., Andres A., Morales E., Camacho J.A., Lens X., Davila S., Mila M., Antignac C., Darnell A., Torra R.
J. Am. Soc. Nephrol. 13:1248-1254(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BFH VAL-985 AND GLU-1015.
[25]"Novel COL4A5, COL4A4, and COL4A3 mutations in Alport syndrome."
Nagel M., Nagorka S., Gross O.
Hum. Mutat. 26:60-60(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS APSAR ASP-532; ARG-739; ARG-853 AND ARG-1216.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X80031 mRNA. Translation: CAA56335.1.
AJ288487 expand/collapse EMBL AC list , AJ288488, AJ288489, AJ288490, AJ288491, AJ288492, AJ288493, AJ288494, AJ288495, AJ288496, AJ288497, AJ288498, AJ288499, AJ288500, AJ288501, AJ288502, AJ288503, AJ288504, AJ288505, AJ288506, AJ288507, AJ288508, AJ288509, AJ288510, AJ288511, AJ288512, AJ288513, AJ288514, AJ288515, AJ288516, AJ288517, AJ288518, AJ288519, AJ288520, AJ288521, AJ288522, AJ288523, AJ288524, AJ288525, AJ288526, AJ288527, AJ288528, AJ288529, AJ288530, AJ288531, AJ288532, AJ288533, AJ288534, AJ288535, AJ288536, AJ288537, AJ288538 Genomic DNA. Translation: CAC36101.1.
AC079235 Genomic DNA. Translation: AAY14671.1.
AC097662 Genomic DNA. Translation: AAY24251.1.
AC107069 Genomic DNA. Translation: AAX93111.1.
AB008496 Genomic DNA. Translation: BAA25064.1.
M81379 mRNA. Translation: AAA51556.1.
M92993 mRNA. Translation: AAA21610.1.
AF258351 mRNA. Translation: AAF72632.1.
U02519 mRNA. Translation: AAA18942.1.
U02520 mRNA. Translation: AAA18943.1.
S55790 mRNA. Translation: AAB19637.1.
L08650 Genomic DNA. Translation: AAA52044.1.
CCDSCCDS42829.1. [Q01955-1]
PIRA49736.
CGHU3B. A54763.
B49736.
S69113.
RefSeqNP_000082.2. NM_000091.4. [Q01955-1]
UniGeneHs.570065.

3D structure databases

ProteinModelPortalQ01955.
SMRQ01955. Positions 1445-1668.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107682. 3 interactions.
IntActQ01955. 1 interaction.
STRING9606.ENSP00000379823.

Chemistry

ChEMBLCHEMBL2364188.

PTM databases

PhosphoSiteQ01955.

Polymorphism databases

DMDM134035067.

Proteomic databases

MaxQBQ01955.
PaxDbQ01955.
PRIDEQ01955.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000396578; ENSP00000379823; ENSG00000169031. [Q01955-1]
GeneID1285.
KEGGhsa:1285.
UCSCuc002vom.2. human. [Q01955-1]

Organism-specific databases

CTD1285.
GeneCardsGC02P227993.
GeneReviewsCOL4A3.
H-InvDBHIX0002893.
HIX0029836.
HGNCHGNC:2204. COL4A3.
HPAHPA042064.
MIM104200. phenotype.
120070. gene.
141200. phenotype.
203780. phenotype.
neXtProtNX_Q01955.
Orphanet88918. Autosomal dominant Alport syndrome.
88919. Autosomal recessive Alport syndrome.
97562. Benign familial hematuria.
PharmGKBPA26719.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG12793.
HOVERGENHBG004933.
KOK06237.
OMASPGCPGK.
OrthoDBEOG7RZ5P3.
PhylomeDBQ01955.
TreeFamTF344135.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_118779. Extracellular matrix organization.

Gene expression databases

ArrayExpressQ01955.
BgeeQ01955.
CleanExHS_COL4A3.
GenevestigatorQ01955.

Family and domain databases

Gene3D2.170.240.10. 1 hit.
InterProIPR016187. C-type_lectin_fold.
IPR008160. Collagen.
IPR001442. Collagen_VI_NC.
[Graphical view]
PfamPF01413. C4. 2 hits.
PF01391. Collagen. 22 hits.
[Graphical view]
SMARTSM00111. C4. 2 hits.
[Graphical view]
SUPFAMSSF56436. SSF56436. 2 hits.
PROSITEPS51403. NC1_IV. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCollagen_alpha-3(IV)_chain.
GenomeRNAi1285.
NextBio5191.
PROQ01955.
SOURCESearch...

Entry information

Entry nameCO4A3_HUMAN
AccessionPrimary (citable) accession number: Q01955
Secondary accession number(s): Q53QQ1 expand/collapse secondary AC list , Q53R14, Q53RW8, Q9BQT2, Q9NYC4, Q9UDJ9, Q9UDK9, Q9UDL0, Q9UDL1
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: March 6, 2007
Last modified: July 9, 2014
This is version 169 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM