Tumor Endothelial Marker Report: TEM11 (nidogen)

	TEM domain structure

	TEM Sequence Analysis

name	from	to	source/E	description
SignalP	1	28	SEG	LCR(L)
unknown	28	106
	42	51	SEG	LCR(DE)
	91	111	toppred2	apolar
NIDO	106	270	SMART, E= 4.75e-62	The domain is described as a extracellular domain with unknown function.
LCR	282	300	SEG	LCR(ED)
EGF	386	426	Pfam, E = 0.0044	Potentially belongs to the sub-type of EGF_Ca domains as it has been predicted by a SmartDB hit.
unknown	426	670		Lipoprotein receptor-related proteins show homology to the following C-terminal part.
	480	500	toppred2	apolar
EGF	668	709	Pfam, E = 0.00011	Potentially belongs to the sub-type of EGF_Ca domains as it has been predicted by a SmartDB hit. Contains a RGD site which has been shown to be a major cell attachment sites in nidogen and that it is recognized by the alphavbeta3 integrin receptor (Dong et al, 1995).
EGF	710	751	Pfam, E = 0.0007	Potentially belongs to the sub-type of EGF_Ca domains as it has been predicted by a SmartDB hit.
EGF	758	801	Pfam, E = 0.0043	Potentially belongs to the sub-type of EGF_Ca domains as it has been predicted by a SmartDB hit.
EGF	802	840	Pfam, E = 2.5e-05	Potentially belongs to the sub-type of EGF_Ca domains as it has been predicted by a SmartDB hit.
thyroglobulin_1	849	919	Pfam, E = 1.4e-32	Belongs to the type-1 Tg domain. Thyroglobulin type 1 repeats are thought to be involved in the control of proteolytic degradation. The six cysteine residue known to be conserved in the Tg type-1a, can be found in TEM11.
apolar	931	951	toppred2
LY	970	1012	SMART, E=5.20e-04	YWTD domains often are bounded by epidermal growth factor (EGF) module The repeats are proposed to fold into a compact beta-propeller structure.
LY	1013	1055	SMART, E=1.01e-15	The YWTD repeats of nidogen functions to bind laminin.
LY	1056	1100	SMART, E=1.32e-14	The YWTD repeats of nidogen functions to bind laminin.
LY	1101	1143	SMART, E=7.46e-05	The YWTD repeats of nidogen functions to bind laminin.
LY	1144	1181	SMART, E=5.97e+01	The YWTD repeats of nidogen functions to bind laminin.
EGF	1208	1244	Pfam, E = 0.6	Potentially belongs to the sub-type of EGF_Ca domains as it has been predicted by a SmartDB hit.
1247

	Remarks

• DOMAIN ARCHITECTURE: The sulfated glycoprotein nidogen is composed of two amino (G1, G2) and one carboxyl (G3) terminal globular domains that are connected by a rod domain composed primarily of endothelial growth factor (EGF) repeats. Due to this structural organization the architectural model is designed as a "dumb-bell" including four major structural domains G1, G2, E, and G3. The rod domain contains is involved in mediating cell adhesion. The amino-terminal G2 domain binds collagen IV,fibronectin and the proteoglycan core (Reinhardt et al 1993), while the C-terminal G3 globule binds to laminin.

• INTERACTIONS:
  • The G3(YWTD) domain binds laminin.The nidogen-laminin binding mediates the connection of laminins to the collagen IV network, perlecan and others.
    • The extracellular matrix laminin-nidogen complex is a ligand for the LAR-FnIII domain 5 (Fn5). The latter could mediate signaling induced by laminin-nidogen, resulting in cell morphological changes.
  • The domain G2 binds collagen IV and heparan sulfate proteoglycan perlecan.

• FUNCTION: It has been proposed that nidogen 1 stabilizes the basement membrane by connecting the laminin and collagen IV networks, and by integrating other proteins, including perlecan. Recent evidence on mouse embryonic stem cells and in C. elegans suggests that nidogen 1 is not required for basement membrane formation or maintenance.
  Independently of the mechanical role in basement membrane assembly nidogen is proposely involved in cell migration. In this context nidogen has been shown to direct axon migration in C.elegans. Modulation of cell behavior is known to be mediated through the integrin receptors that recognize specific sequences in the constituent molecules of the basement membrane. Two cell interaction sites are known for nidogen: the RGD motif in the second EGF domain, and a sequence including the first EGF repeat. The role of the RGD sequence in entactin in trophoblast outgrowth supports the assumption that this sequence is involved in modification of the cytoskeleton (Yelianet al, 1993) .

• HOMOLOGUES:
  • Multiple proteins homologous over the whole length are known in C. elegans, H. sapiens, M. musculus, Rattus, Halocynthia.
  • The COOH-terminal globular domain shows homology to the EGF precursor and the low density lipoprotein receptor.

	Sequence Information

TEM	TEM11
Reliability of Gen2Tag mapping	Cid->tag (Hs.62041) frequency: tem11: CATG-ATTTTGTATGA=59/71        CATG-TAGGTCTTTT=8/71
Analysis	BlastP against nr Output Created by a Suite of Single Sequence Analysis Techniques
Protein Description	SEQ.SOURCE: sp|P14543|NIDO_HUMAN NIDOGEN PRECURSOR (ENTACTIN) - Homo sapiens (Human). DOMAIN 29 669 LARGER GLOBULAR DOMAIN. DOMAIN 670 917 CYSTEINE-RICH. DOMAIN 918 1247 SMALLER GLOBULAR DOMAIN.
Protein Sequence	MLASSSRIRAAWTRALLLPLLLAGPVGCLSRQELFPFGPGQGDLELEDGDDFVSPALELSGALRFYDRSD IDAVYVTTNGIIATSEPPAKESHPGLFPPTFGAVAPFLADLDTTDGLGKVYYREDLSPSITQRAAECVHR GFPEISFQPSSAVVVTWESVAPYQGPSRDPDQKGKRNTFQAVLASSDSSSYAIFLYPEDGLQFHTTFSKK ENNQVPAVVAFSQGSVGFLWKSNGAYNIFANDRESIENLAKSSNSGQQGVWVFEIGSPATTNGVVPADVI LGTEDGAEYDDEDEDYDLATTRLGLEDVGTTPFSYKALRRGGADTYSVPSVLSPRRAATERPLGPPTERT RSFQLAVETFHQQHPQVIDVDEVEETGVVFSYNTDSRQTCANNRHQCSVHAECRDYATGFCCSCVAGYTG NGRQCVAEGSPQRVNGKVKGRIFVGSSQVPIVFENTDLHSYVVMNHGRSYTAISTIPETVGYSLLPLAPV GGIIGWMFAVEQDGFKNGFSITGGEFTRQAEVTFVGHPGNLVIKQRFSGIDEHGHLTIDTELEGRVPQIP FGSSVHIEPYTELYHYSTSVITSSSTREYTVTEPERDGASPSRIYTYQWRQTITFQECVHDDSRPALPST QQLSVDSVFVLYNQEEKILRYAFSNSIGPVREGSPDALQNPCYIGTHGCDTNAACRPGPRTQFTCECSIG FRGDGRTCYDIDECSEQPSVCGSHTICNNHPGTFRCECVEGYQFSDEGTCVAVVDQRPINYCETGLHNCD IPQRAQCIYTGGSSYTCSCLPGFSGDGQACQDVDECQPSRCHPDAFCYNTPGSFTCQCKPGYQGDGFRCV PGEVEKTRCQHEREHILGAAGATDPQRPIPPGLFVPECDAHGHYAPTQCHGSTGYCWCVDRDGREVEGTR TRPGMTPPCLSTVAPPIHQGPAVPTAVIPLPPGTHLLFAQTGKIERLPLEGNTMRKTEAKAFLHVPAKVI IGLAFDCVDKMVYWTDITEPSIGRASLHGGEPTTIIRQDLGSPEGIAVDHLGRNIFWTDSNLDRIEVAKL DGTQRRVLFETDLVNPRGIVTDSVRGNLYWTDWNRDNPKIETSYMDGTNRRILVQDDLGLPNGLHFDAFS SQLCWVDAGTNRAECLNPSQPSRRKALEGLQYPFAVTSYGKNLYFTDWKMNSVVALDLAISKETDAFQPH KQTRLYGITTALSQCPQGHNYCSVNNGGCTHLCLATPGSRTCRCPDNTLGVDCIERK
SAGE-Tag	CATG-ATTTTGTATGA
EST/cluster Description	UNIGEN CLUSTER: UniGene Cluster Hs.62041 NID SEQ.SOURCE: gi|189208|gb|M30269.1|HUMNID Human nidogen mRNA, complete cds MARKINGS: tem11 Tag in red first Poly-A-signal following the tem31 Tag in bold
EST/cluster Sequence	1 ATGTTGGCCTCGAGCAGCCGGATCCGGGCTGCGTGGACGCGGGCGCTGCTGCTGCCGCTG 61 CTGCTGGCGGGGCCTGTGGGCTGCCTGAGCCGCCAGGAGCTCTTTCCCTTCGGCCCCGGA 121 CAGGGGGACCTGGAGCTGGAGGACGGGGATGACTTCGTCTCTCCTGCCCTGGAGCTGAGT 181 GGGGCGCTCCGCTTCTACGACAGATCCGACATCGACGCAGTCTACGTCACCACAAATGGC 241 ATCATTGCTACGAGTGAACCCCCGGCCAAAGAATCCCATCCCGGGCTCTTCCCACCAACA 301 TTCGGTGCAGTCGCCCCTTTCCTGGCGGACTTGGACACGACCGATGGCCTGGGGAAGGTT 361 TATTATCGAGAAGACTTATCCCCCTCCATCACTCAGCGAGCAGCAGAGTGTGTCCACAGA 421 GGGTTCCCGGAGATCTCTTTCCAGCCTAGTAGCGCGGTGGTTGTCACTTGGGAATCCGTG 481 GCCCCCTACCAAGGGCCCAGCAGGGACCCAGACCAGAAAGGCAAGAGAAACACGTTCCAG 541 GCTGTTCTAGCCTCCTCTGATTCCAGCTCCTATGCCATTTTCCTTTATCCTGAGGATGGT 601 CTGCAGTTCCATACGACATTCTCAAAGAAGGAAAACAACCAAGTTCCTGCCGTGGTTGCA 661 TTCAGTCAAGGTTCAGTGGGATTCTTATGGAAGAGCAACGGAGCTTATAACATATTTGCT 721 AATGACAGGGAATCAATTGAAAATTTGGCCAAGAGTAGTAACTCTGGGCAGCAGGGTGTC 781 TGGGTGTTTGAGATTGGGAGTCCAGCCACCACCAATGGCGTGGTGCCTGCAGACGTGATC 841 CTCGGAACTGAAGATGGGGCAGAGTATGATGATGAGGATGAAGATTATGACCTGGCGACC 901 ACTCGTCTGGGCCTGGAGGATGTGGGCACCACGCCCTTCTCCTACAAGGCTCTGAGAAGG 961 GGAGGTGCTGACACATACAGTGTGCCCAGCGTCCTCTCCCCGCGCCGGGCAGCTACCGAA 1021 AGGCCCCTTGGACCTCCCACAGAGAGAACCAGGTCTTTCCAGTTGGCAGTGGAGACTTTT 1081 CACCAGCAGCACCCTCAGGTCATAGATGTGGATGAAGTTGAGGAAACAGGAGTTGTTTTC 1141 AGCTATAACACGGATTCCCGCCAGACGTGTGCTAACAACAGACACCAGTGCTCGGTGCAC 1201 GCAGAGTGCAGGGACTACGCCACGGGCTTCTGCTGCAGCTGTGTCGCTGGCTATACGGGC 1261 AATGGCAGGCAATGTGTTGCAGAAGGTTCCCCCCAGCGAGTCAATGGCAAGGTGAAAGGA 1321 AGGATCTTTGTGGGGAGCAGCCAGGTCCCCATTGTCTTTGAGAACACTGACCTCCACTCT 1381 TACGTAGTAATGAACCACGGGCGCTCCTACACAGCCATCAGCACCATTCCCGAGACCGTT 1441 GGATATTCTCTGCTTCCACTGGCCCCAGTTGGAGGCATCATTGGATGGATGTTTGCAGTG 1501 GAGCAGGACGGATTCAAGAATGGGTTCAGCATCACCGGGGGTGAGTTCACTCGCCAGGCT 1561 GAGGTGACCTTCGTGGGGCACCCGGGCAATCTGGTCATTAAGCAGCGGTTCAGCGGCATC 1621 GATGAGCATGGGCACCTGACCATCGACACGGAGCTGGAGGGCCGCGTGCCGCAGATTCCG 1681 TTCGGCTCCTCCGTGCACATTGAGCCCTACACGGAGCTGTACCACTACTCCACCTCAGTG 1741 ATCACTTCCTCCTCCACCCGGGAGTACACGGTGACTGAGCCCGAGCGAGATGGGGCATCT 1801 CCTTCACGCATCTACACTTACCAGTGGCGCCAGACCATCACCTTCCAGGAATGCGTCCAC 1861 GATGACTCCCGGCCAGCCCTGCCCAGCACCCAGCAGCTCTCGGTGGACAGCGTGTTCGTC 1921 CTGTACAACCAGGAGGAGAAGATCTTGCGCTACGCTTTCAGCAACTCCATTGGGCCTGTG 1981 AGGGAAGGCTCCCCTGATGCTCTTCAGAATCCCTGCTACATCGGCACTCATGGGTGTGAC 2041 ACCAACGCGGCCTGTCGCCCTGGTCCCAGGACACAGTTCACCTGCGAGTGCTCCATCGGC 2101 TTCCGAGGAGACGGGCGAACCTGCTATGATATTGATGAATGTTCAGAACAACCCTCAGTG 2161 TGTGGGAGCCACACAATCTGCAATAATCACCCAGGAACCTTCCGCTGCGAGTGTGTGGAG 2221 GGCTACCAGTTTTCAGATGAGGGAACGTGTGTGGCTGTCGTGGACCAGCGCCCCATCAAC 2281 TACTGTGAAACTGGCCTTCATAACTGCGACATACCCCAGCGGGCCCAGTGTATCTACACA 2341 GGAGGCTCCTCCTACACCTGTTCCTGCTTGCCAGGCTTTTCTGGGGATGGCCAAGCCTGC 2401 CAAGATGTAGATGAATGCCAGCCAAGCCGATGTCACCCTGACGCCTTCTGCTACAACACT 2461 CCAGGCTCTTTCACGTGCCAGTGCAAACCTGGTTATCAGGGAGACGGCTTCCGTTGCGTG 2521 CCCGGAGAGGTGGAGAAAACCCGGTGCCAGCACGAGCGAGAACACATTCTCGGGGCAGCG 2581 GGGGCGACAGACCCACAGCGACCCATTCCTCCGGGGCTGTTCGTTCCTGAGTGCGATGCG 2641 CACGGGCACTACGCGCCCACCCAGTGCCACGGCAGCACCGGCTACTGCTGGTGCGTGGAT 2701 CGCGACGGCCGCGAGGTGGAGGGCACCAGGACCAGGCCCGGGATGACGCCCCCGTGTCTG 2761 AGTACAGTGGCTCCCCCGATTCACCAAGGACCTGCGGTGCCTACCGCCGTGATCCCCTTG 2821 CCTCCTGGGACCCATTTACTCTTTGCCCAGACTGGGAAGATTGAGCGCCTGCCCCTGGAG 2881 GGAAATACCATGAGGAAGACAGAAGCAAAGGCGTTCCTTCATGTCCCGGCTAAAGTCATC 2941 ATTGGACTGGCCTTTGACTGCGTGGACAAGATGGTTTACTGGACGGACATCACTGAGCCT 3001 TCCATTGGGAGAGCTAGTCTACATGGTGGAGAGCCAACCACCATCATTAGACAAGATCTT 3061 GGAAGTCCAGAAGGTATCGCTGTTGATCACCTTGGCCGCAACATCTTCTGGACAGACTCT 3121 AACCTGGATCGAATAGAAGTGGCGAAGCTGGACGGCACGCAGCGCCGGGTGCTCTTTGAG 3181 ACTGACCTGGTGAATCCCAGAGGCATTGTAACGGATTCCGTGAGAGGGAACCTTTACTGG 3241 ACAGACTGGAACAGAGATAACCCCAAGATTGAAACTTCCTACATGGACGGCACGAACCGG 3301 AGGATCCTTGTGCAGGATGACCTGGGCTTGCCCAATGGACTGACCTTCGATGCGTTCTCA 3361 TCTCAGCTCTGCTGGGTGGATGCAGGCACCAATCGGGCGGAATGCCTGAACCCCAGTCAG 3421 CCCAGCAGACGCAAGGCTCTCGAAGGGCTCCAGTATCCTTTTGCTGTGACGAGCTACGGG 3481 AAGAATCTGTATTTCACAGACTGGAAGATGAATTCCGTGGTTGCTCTCGATCTTGCAATT 3541 TCCAAGGAGACGGATGCTTTCCAACCCCACAAGCAGACCCGGCTGTATGGCATCACCACG 3601 GCCCTGTCTCAGTGTCCGCAAGGCCATAACTACTGCTCAGTGAACAATGGCGGCTGCACC 3661 CACCTATGCTTGGCCACCCCAGGGAGCAGGACCTGCCGTTGCCCTGACAACACCTTGGGA 3721 GTTGACTGTATCGAACAGAAATGAAGACAAGAGTGCCTTATTTCCTTTCCAAGTATTTCA 3781 CAGCAACACTCTACTTGAAGCAACTTGGTCCAGATTGAAAAGTGTCCTCTGGCTGAGTGG 3841 CCACTAGGCCCAGACCCAGCCCAGCCTGAGCCCCAACAACAACTTTTCCCTCACTGTTCC 3901 CCAAAACATGCACCCTGGACTTCTCTAATAGAAAAGTCTCCACCCCTACACAAGGACAGA 3961 ACCCTCCACCCCTACCCCCAACCCTCAGACAGACTTATACACCCCTGAGTGAGGATTACA 4021 TGCCCATCCCAGTGTCCTAGGACCTTTTCCCAATACTAGCCCCCCAGTGGTGAACAGAAC 4081 CTCCCAAATTTGAGTTGCACCCTTCCCTGTGGCCTTATGAGCTCAGCCTCGCTTTGAGGT 4141 ACCCACCGTCCTGTCAGCTCCTTGACCTATGAGCTGGGGCCTGACTAGGAAAAGTTGGGA 4201 GTTAAGGAGGAAATTAGCATTCCTTAATGTTTTGTTTTGGTGCTCTGAATTTCTTCTTTA 4261 TTATAGTCCTATAGTTTTACTCCTCAGTTCCTCACCATCATCATCTTGTCTAAGACCCCC 4321 ATTATAATATTCATGCGCTGCTTTTTCATCAAAACCTACCCTGTCCTAGAGATCTATGGG 4381 CATTTGGTGGATGATAATGAGCAGCCCCTCCCAGATAGAATGTCAATATTTGAGCAGTAG 4441 GATATTGGCATTTGTTAGTTAAAGGCTTAAATCAAAAGAATGTCCAATGGTAGGAATTTC 4501 AAGGTGTAGGTCAGATATTTGAGAATAGGGGATTTTTTTGATGTGCCTTAAATTATACCA 4561 AAGATTACTAATTATTCCTCTTTGCCCAAAATACTTGCATCCAAGGTTCTAGTCTCTGTT 4621 GCTGTGCTGGTCTTTAGCCCCACTGCTGGCACTGATGTCCCTCCTTTTCACGGAGACCTA 4681 TCTGAGGTACAGGATGGGGCTGGCACCAGATGATGTCCCACCACAGTCCCTCACCTCCGG 4741 CCTCCACATGACAGAACCAATTTACACTCAACCATGACCTCACCCCTCCTTGGTTTCTCC 4801 CTCGATCTGGTGGCCCTTTTTGGATGTATTCTTATCTAACAACACAATCCGGAAAGACTG 4861 AATTGAATATTTATACTAATGGTTCATATCCTTTATTGCTCAATGATCTAATTAAAGGGA 4921 TCATTGCCACATTTCATGTTTATATTTCTACAATTTGTTTAGAAAACATCTCCTGACCAT 4981 ATCAGTAGCTCGTGTTATCTTTTTATCAACTGCTTCCCAGAGTCCTAAAACAATAGAAAT 5041 TTTGGATTGAAAAGTTCAGCATAAGGAGTTTGAGTCAGTAAAGGATGGGATAAAGGAGTC 5101 GAGATGATTCAATGAAAAGTATCACAAAAAAGAGATTGATCAACAAGAGAAATAAAAAAG 5161 CCCAAGAGGAAGTGGTAGGGGAAGGAATTTAAGAACAGCAATAAGTAAAACTCTTAAGTA 5221 ACTCCAAAAAGAAAATGGTACATTTTGCCAAAGACCACTTATACTTGAGAACATGGAAGA 5281 ATTTGCCTGATACTCTCTTTGGGGAAAAGAGTCTCTCCTCTTTTCCTCAAACCCCAGTAC 5341 ACTCAGCCTCTCTGCCCCACCTTCTCCTGACTTTGTCCTCACTTGCTTCTGCAGTACATT 5401 GGAACCTGAATTGAAAGAAAGTCTTCCTTGGAATAATTGGAGTTTGTCTTGAGAGGCAAA 5461 TATAGCCCCAAGAATCACAAGATTCGAGGACCATGTAGGTCTTTTACGTAGCCCAAATCC 5521 ATAAATTAGTCTCACTTTTTGTATTTATCGTTTCATATTAAACCCTCTATATCAAATGTT 5581 CATCATGATTTTGTATGATTTTTATAACTATTTTATTCATTTTATTAGATTTATTCTAAA 5641 ATTTTTTAATGGTAAATTCTTAAACTGTGGAAACCACTGAAGGTGCTTATTAACTGTTCT 5701 CCCAGATTTGTACAAGTATTGGATGATTCCTTGAGTTTACAGCTGTACAAATAGTGTGGA 5761 AAATAAACTTTTTTAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAACTCGAGGGGGG 5821 GCCCGGTACCCAATTCGCCCTATAGTGAGTCGTATTACAATTCACTGGCCGACGTTTTAC 5881 AACGTCGTGACTGGG
Genomic Sequence Description
Genomic Sequence

	Literature

PubMed:11071916	Nidogen Is Nonessential and Not Required for Normal Type IV Collagen Localization in Caenorhabditis elegans. Kang SH, Kramer JM. Mol Biol Cell. 2000 Nov;11(11):3911-3923.
PubMed:2574658	The absence of nidogen 1 does not affect murine basement membrane formation. Murshed M, Smyth N, Miosge N, Karolat J, Krieg T, Paulsson M, Nischt R Mol Cell Biol 2000 Sep;20(18):7007-12
PubMed:20217227	Positioning of longitudinal nerves in C. elegans by nidogen. S. Kim, et al. Science 2000 Apr 7;288(5463):150-4.
PubMed:9790844	An extracellular beta-propeller module predicted in lipoprotein and scavenger receptors, tyrosine kinases, epidermal growth factor precursor, and extracellular matrix components. Springer TA. J Mol Biol. 1998 Nov 6;283(4):837-62
PubMed:8496153	Mapping of nidogen binding sites for collagen type IV, heparan sulfate proteoglycan, and zinc. Reinhardt D, Mann K, Nischt R, Fox JW, Chu ML, Krieg T, Timpl R. J Biol Chem. 1993 May 25;268(15):10881-7.
PubMed:1717261	Recombinant nidogen consists of three globular domains and mediates binding of laminin to collagen type IV. Fox JW, Mayer U, Nischt R, Aumailley M, Reinhardt D, Wiedemann H, Mann K, Timpl R, Krieg T, Engel J, et al. EMBO J. 1991 Nov;10(11):3137-46.
PubMed:2574658	Human nidogen: complete amino acid sequence and structural domains deduced from cDNAs, and evidence for polymorphism of the gene. Nagayoshi T, Sanborn D, Hickok NJ, Olsen DR, Fazio MJ, Chu ML, Knowlton R, Mann K, Deutzmann R, Timpl R, et al. DNA. 1989 Oct;8(8):581-94.