EF-hand, extracellular calcium-binding (EC) motif, found in secreted modular calcium-binding protein SMOC-1, SMOC-2, and similar proteins; SMOC proteins corresponds to a group matricellular proteins that are involved in direct or indirect modulation of growth factor signaling pathways and play diverse roles in physiological processes involving extensive tissue remodeling, migration, proliferation, and angiogenesis. They may mediate intercellular signaling and cell type-specific differentiation during gonad and reproductive tract development. SMOC-1 is localized in basement membranes. Its mutations have been found to be associated with individuals with Warrdenburg Anopthalmia Syndrome. SMOC-2 is ubiquitously expressed and is involved in angiogenesis and the regulation of cell cycle progression. It enhances the angiogenic effect of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). It has also been implicated in generalized vitiligo. SMOC proteins consist of a follistatin-like (FS) domain, two thyroglobulin-like (TY) domains, a novel domain conserved only in SMOC proteins, and an extracellular calcium-binding (EC) domain with two EF-hand calcium-binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161076496 382 CTEPRKTQFLKELKAYLNTSLLPSSTTGSnSSMWKTDDERIATLSFVYLDKNKNKSWDRREWKNFRDLVTSASHLRRCGK 461
Cdd:cd16234    1 CPEAKKTEFLNNLIDALKTEMVRSGNSNS-SAPDKSSEEQVLDWKFSQLDKNKNGVLERKEWKPFKRLLKKAVKPKKCAR 79

                         90       100
                 ....*....|....*....|...
gi 161076496 462 KMPRYCDVNGDKKISLAEWLNCL 484
Cdd:cd16234   80 KFPKYCDVNKDKKISLTEWLNCL 102

Thyroglobulin type I repeats.; The N-terminal region of human thyroglobulin contains 11 type-1 repeats TY repeats are proposed to be inhibitors of cysteine proteases

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 161076496 303 CWMDQSVTLEEQGHGGKSVLFVPQCLPDGRYQRIQCYssTSTSYCWCVNEDtGKSIPGTSVKNKRPQC 370
Cdd:cd00191    2 CERERASALESLAGPKLSGLYVPQCDEDGNYEPVQCH--GSTGYCWCVDPD-GEEIPGTRTRGGPPNC 66

Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the cognate enzyme as substrate. The reactive site peptide bond is a combining loop which has an identical conformation in all Kazal inhibitors and in all enzyme/inhibitor complexes. These Kazal domains (small hydrophobic core of alpha/beta structure with 3 to 4 disulfide bonds) often occur in tandem arrays. Similar domains are also present in follistatin (FS) and follistatin-like family members, which play an important role in tissue specific regulation. The FS domain consists of an N-terminal beta hairpin (FOLN/EGF-like domain) and a Kazal-like domain and has five disulfide bonds. Although the Kazal-like FS substructure is similar to Kazal proteinase inhibitors, no FS domain has yet been shown to be a proteinase inhibitor. Follistatin-like family members include SPARC, also known as, BM-40 or osteonectin, the Gallus gallus Flik protein, as well as, agrin which has a long array of FS domains. The kazal-type inhibitor domain has also been detected in an extracellular loop region of solute carrier 21 (SLC21) family members (organic anion transporters) , which may regulate the specificity of anion uptake. The distant homolog, Ascidian trypsin inhibitor, is included in this CD.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 161076496  38 CDDNEGPVCGTDGQTYPTRCHLLRAQC-GGHQVSLKYSGSC 77
Cdd:cd00104    1 CPKEYDPVCGSDGKTYSNECHLGCAACrSGRSITVAHNGPC 41

EF-hand, extracellular calcium-binding (EC) motif, found in secreted modular calcium-binding protein SMOC-1, SMOC-2, and similar proteins; SMOC proteins corresponds to a group matricellular proteins that are involved in direct or indirect modulation of growth factor signaling pathways and play diverse roles in physiological processes involving extensive tissue remodeling, migration, proliferation, and angiogenesis. They may mediate intercellular signaling and cell type-specific differentiation during gonad and reproductive tract development. SMOC-1 is localized in basement membranes. Its mutations have been found to be associated with individuals with Warrdenburg Anopthalmia Syndrome. SMOC-2 is ubiquitously expressed and is involved in angiogenesis and the regulation of cell cycle progression. It enhances the angiogenic effect of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). It has also been implicated in generalized vitiligo. SMOC proteins consist of a follistatin-like (FS) domain, two thyroglobulin-like (TY) domains, a novel domain conserved only in SMOC proteins, and an extracellular calcium-binding (EC) domain with two EF-hand calcium-binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161076496 382 CTEPRKTQFLKELKAYLNTSLLPSSTTGSnSSMWKTDDERIATLSFVYLDKNKNKSWDRREWKNFRDLVTSASHLRRCGK 461
Cdd:cd16234    1 CPEAKKTEFLNNLIDALKTEMVRSGNSNS-SAPDKSSEEQVLDWKFSQLDKNKNGVLERKEWKPFKRLLKKAVKPKKCAR 79

                         90       100
                 ....*....|....*....|...
gi 161076496 462 KMPRYCDVNGDKKISLAEWLNCL 484
Cdd:cd16234   80 KFPKYCDVNKDKKISLTEWLNCL 102

Thyroglobulin type I repeats.; The N-terminal region of human thyroglobulin contains 11 type-1 repeats TY repeats are proposed to be inhibitors of cysteine proteases

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 161076496 303 CWMDQSVTLEEQGHGGKSVLFVPQCLPDGRYQRIQCYssTSTSYCWCVNEDtGKSIPGTSVKNKRPQC 370
Cdd:cd00191    2 CERERASALESLAGPKLSGLYVPQCDEDGNYEPVQCH--GSTGYCWCVDPD-GEEIPGTRTRGGPPNC 66

Thyroglobulin type I repeats; The N-terminal region of human thyroglobulin contains 11 type-1 repeats TY repeats are proposed to be inhibitors of cysteine proteases and binding partners of heparin.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 161076496   324 VPQCLPDGRYQRIQCYssTSTSYCWCVNEdTGKSIPGTSVKNKRPQCDE 372
Cdd:smart00211   1 IPQCDEDGNYEPVQCD--GSSGQCWCVDA-TGREIPGTRTEGGDPDCPS 46

Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the cognate enzyme as substrate. The reactive site peptide bond is a combining loop which has an identical conformation in all Kazal inhibitors and in all enzyme/inhibitor complexes. These Kazal domains (small hydrophobic core of alpha/beta structure with 3 to 4 disulfide bonds) often occur in tandem arrays. Similar domains are also present in follistatin (FS) and follistatin-like family members, which play an important role in tissue specific regulation. The FS domain consists of an N-terminal beta hairpin (FOLN/EGF-like domain) and a Kazal-like domain and has five disulfide bonds. Although the Kazal-like FS substructure is similar to Kazal proteinase inhibitors, no FS domain has yet been shown to be a proteinase inhibitor. Follistatin-like family members include SPARC, also known as, BM-40 or osteonectin, the Gallus gallus Flik protein, as well as, agrin which has a long array of FS domains. The kazal-type inhibitor domain has also been detected in an extracellular loop region of solute carrier 21 (SLC21) family members (organic anion transporters) , which may regulate the specificity of anion uptake. The distant homolog, Ascidian trypsin inhibitor, is included in this CD.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 161076496  38 CDDNEGPVCGTDGQTYPTRCHLLRAQC-GGHQVSLKYSGSC 77
Cdd:cd00104    1 CPKEYDPVCGSDGKTYSNECHLGCAACrSGRSITVAHNGPC 41

Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and follistatin-like domains.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 161076496    37 ECDDNEGPVCGTDGQTYPTRCHLLRAQC-GGHQVSLKYSGSC 77
Cdd:smart00280   5 ACPREYDPVCGSDGVTYSNECHLCKAACeSGKSIEVKHDGPC 46

Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulphides.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 161076496   38 CDDNEG-PVCGTDGQTYPTRCHLLRAQCGGHQVS----LKYSGSC 77
Cdd:pfam07648   6 CPKTEYePVCGSDGVTYPSPCALCAAGCKLGKEVkeekVKYDGSC 50

EF-hand, extracellular calcium-binding (EC) motif, found in secreted modular calcium-binding protein SMOC-1, SMOC-2, and similar proteins; SMOC proteins corresponds to a group matricellular proteins that are involved in direct or indirect modulation of growth factor signaling pathways and play diverse roles in physiological processes involving extensive tissue remodeling, migration, proliferation, and angiogenesis. They may mediate intercellular signaling and cell type-specific differentiation during gonad and reproductive tract development. SMOC-1 is localized in basement membranes. Its mutations have been found to be associated with individuals with Warrdenburg Anopthalmia Syndrome. SMOC-2 is ubiquitously expressed and is involved in angiogenesis and the regulation of cell cycle progression. It enhances the angiogenic effect of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). It has also been implicated in generalized vitiligo. SMOC proteins consist of a follistatin-like (FS) domain, two thyroglobulin-like (TY) domains, a novel domain conserved only in SMOC proteins, and an extracellular calcium-binding (EC) domain with two EF-hand calcium-binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161076496 382 CTEPRKTQFLKELKAYLNTSLLPSSTTGSnSSMWKTDDERIATLSFVYLDKNKNKSWDRREWKNFRDLVTSASHLRRCGK 461
Cdd:cd16234    1 CPEAKKTEFLNNLIDALKTEMVRSGNSNS-SAPDKSSEEQVLDWKFSQLDKNKNGVLERKEWKPFKRLLKKAVKPKKCAR 79

                         90       100
                 ....*....|....*....|...
gi 161076496 462 KMPRYCDVNGDKKISLAEWLNCL 484
Cdd:cd16234   80 KFPKYCDVNKDKKISLTEWLNCL 102

Thyroglobulin type I repeats.; The N-terminal region of human thyroglobulin contains 11 type-1 repeats TY repeats are proposed to be inhibitors of cysteine proteases

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 161076496 303 CWMDQSVTLEEQGHGGKSVLFVPQCLPDGRYQRIQCYssTSTSYCWCVNEDtGKSIPGTSVKNKRPQC 370
Cdd:cd00191    2 CERERASALESLAGPKLSGLYVPQCDEDGNYEPVQCH--GSTGYCWCVDPD-GEEIPGTRTRGGPPNC 66

EF-hand, extracellular calcium-binding (EC) motif, found in secreted modular calcium-binding protein 2 (SMOC-2); SMOC-2, also termed SPARC-related modular calcium-binding protein 2, or smooth muscle-associated protein 2 (SMAP-2), is a ubiquitously expressed matricellular protein that enhances the response to angiogenic growth factors, mediate cell adhesion, keratinocyte migration, and metastasis. It is also associated with vitiligo and craniofacial and dental defects. Moreover, SMOC-2 acts as an Arf1 GTPase-activating protein (GAP) that interacts with clathrin heavy chain (CHC) and clathrin assembly protein CALM and functions in the retrograde, early endosome/trans-Golgi network (TGN) pathway in a clathrin- and AP-1-dependent manner. It also contributes to mitogenesis via activation of integrin-linked kinase (ILK). SMOC-2 contains a follistatin-like (FS) domain, two thyroglobulin-like (TY) domains, a novel domain, which is found only in the homologous SMOC-1, and an extracellular calcium-binding (EC) domain with two EF-hand calcium-binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161076496 382 CTEPRKTQFLKELKAYLNTSLL-----PSSTTG--SNSSMWKTDDERIATLSFVYLDKNKNKSWDRREWKNFRDLVTSAS 454
Cdd:cd16241    1 CPGAKKTEFLTSVLDALSTDMVhavsdPSASSRrlSEPDPSHTLEERVVHWYFKQLDKNSSGDIGKKEIKPFKRFLRKKS 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 161076496 455 HLRRCGKKMPRYCDVNGDKKISLAEWLNCLQAT 487
Cdd:cd16241   81 KPKKCVKKFVEYCDVNNDKSLSVQELMGCLGVT 113

EF-hand, extracellular calcium-binding (EC) motif, found in secreted modular calcium-binding protein 2 (SMOC-2); SMOC-2, also termed SPARC-related modular calcium-binding protein 2, or smooth muscle-associated protein 2 (SMAP-2), is a ubiquitously expressed matricellular protein that enhances the response to angiogenic growth factors, mediate cell adhesion, keratinocyte migration, and metastasis. It is also associated with vitiligo and craniofacial and dental defects. Moreover, SMOC-2 acts as an Arf1 GTPase-activating protein (GAP) that interacts with clathrin heavy chain (CHC) and clathrin assembly protein CALM and functions in the retrograde, early endosome/trans-Golgi network (TGN) pathway in a clathrin- and AP-1-dependent manner. It also contributes to mitogenesis via activation of integrin-linked kinase (ILK). SMOC-2 contains a follistatin-like (FS) domain, two thyroglobulin-like (TY) domains, a novel domain, which is found only in the homologous SMOC-1, and an extracellular calcium-binding (EC) domain with two EF-hand calcium-binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161076496 182 CSKSDRSQFNTNLMRMFRNEAQSFFRQPSLSD--------SHILE-----WQFSKLDTNGNKLLDRQEIRELKKVLRRNV 248
Cdd:cd16241    1 CPGAKKTEFLTSVLDALSTDMVHAVSDPSASSrrlsepdpSHTLEervvhWYFKQLDKNSSGDIGKKEIKPFKRFLRKKS 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 161076496 249 KPRRCGRTFGKYCDVTKDANLNWLEWSVCF 278
Cdd:cd16241   81 KPKKCVKKFVEYCDVNNDKSLSVQELMGCL 110

EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich in cysteine (SPARC)-like proteins; The SPARC protein family represents a diverse group of proteins that share a follistatin-like (FS) domain and an extracellular calcium-binding (EC) domain with two EF-hand motifs. It includes SPARC (for secreted protein acidic and rich in cysteine, also termed osteonectin/ON, or basement-membrane protein 40/BM-40), SPARC-like protein 1 (for secreted protein, acidic and rich in cysteines-like 1/ SPARCL1, also termed high endothelial venule protein/Hevi, or MAST 9, or SC-1, or RAGS-1, or QR1, or ECM 2), testicans 1, 2, and 3 (also termed SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycans, or SPOCK), secreted modular calcium-binding protein SMOC-1 (also termed SPARC-related modular calcium-binding protein 1) and SMOC-2 (also termed SPARC-related modular calcium-binding protein 2, or smooth muscle-associated protein 2/SMAP-2), follistatin-related protein 1 (FRP-1, also termed follistatin-like protein 1/fstl-1, TSC-36/Flik, TGF-beta inducible protein). The SPARC proteins have been implicated in modulating cell interaction with the extracellular milieu, including regulation of extracellular matrix assembly and deposition, counter-adhesion, effects on extracellular protease activity, and modulation of growth factor/cytokine signaling pathways, as well as in development and disease.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161076496 182 CSKSDRSQFNTNLMRMF-----RNEAQSFFRQPSLSD------SHILEWQFSKLDTNGNKLLDRqeiRELKKVLRRNVKP 250
Cdd:cd00252    1 CPGSELMQFPDRLLDWLlllkeQDENRSYDNNKRGHDlsgtmrKEIAQWEFDNLDNNKDGKLDK---RELAPFRAPLMPL 77

                         90       100
                 ....*....|....*....|....*....
gi 161076496 251 RRCGRTFGKYCDVTKDANLNWLEWSVCFT 279
Cdd:cd00252   78 EHCARGFFESCDLNKDKKISLQEWLGCFG 106

EF-hand, extracellular calcium-binding (EC) motif, found in secreted modular calcium-binding protein 1 (SMOC-1); SMOC-1, also termed SPARC-related modular calcium-binding protein 1, or smooth muscle-associated protein 1 (SMAP-1), is an Arf6 GTPase-activating protein (GAP) that directly interacts with clathrin and regulates the clathrin-dependent endocytosis of transferrin receptors from the plasma membrane. It is predominantly localized in basement membranes. SMOC-1 acts as a regulator of osteoblast differentiation and is involved in inhibition of transforming growth factor-beta (TGF-beta) signaling through production of nitric oxide. It also plays an essential role in ocular and limb development and functions as a regulator of bone morphogenic protein (BMP) signaling. It interacts with a matricellular protein, tenascin C in addition to the serum proteins, fibulin-1 and C-reactive protein, but not collagens. Two point mutations in the SMOC1 gene may cause Waardenburg Anophtalmia Syndrome. Moreover, SMOC-1 is involved in direct or indirect modulation of growth factor signaling pathways and plays a role in physiological processes involving extensive tissue remodeling. SMOC-1 contains a follistatin-like (FS) domain, two thyroglobulin-like (TY) domains, a novel domain, which is found only in the homologous SMOC-2, and an extracellular calcium-binding (EC) domain with two EF-hand calcium-binding motifs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161076496 382 CTEPRKTQFLKELKAYLNTSLL-----PSSTTG---SNSSMWKTDDERIATLSFVYLDKNKNKSWDRREWKNFRDLVTSA 453
Cdd:cd16240    1 CPEGKKLEFITSLLDALTTDMVqainsAAPTGGgrfSEPDPSHTLEERVVHWYFSQLDNNSSNDINKKELKPFKRYVKKK 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 161076496 454 SHLRRCGKKMPRYCDVNGDKKISLAEWLNCL 484
Cdd:cd16240   81 AKPKKCARRFTDYCDLNKDKSISLQELKGCL 111

Thyroglobulin type-1 repeat; Thyroglobulin type 1 repeats are thought to be involved in the control of proteolytic degradation. The domain usually contains six conserved cysteines. These form three disulphide bridges. Cysteines 1 pairs with 2, 3 with 4 and 5 with 6.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 161076496   89 RQQERDPGYFVPRCRKDGNFAAMQCYGNNG-CWCSDSQGRPIAD 131
Cdd:pfam00086  13 ASGRPASGLYIPNCDEDGFYKPVQCHGSTGyCWCVDPEGQEIPG 56

Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and follistatin-like domains.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 161076496    37 ECDDNEGPVCGTDGQTYPTRCHLLRAQC-GGHQVSLKYSGSC 77
Cdd:smart00280   5 ACPREYDPVCGSDGVTYSNECHLCKAACeSGKSIEVKHDGPC 46

EF-hand, extracellular calcium-binding (EC) motif, found in testican-3 (TICN3); TICN3, also termed SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 3 (Spock3), is a brain-specific heparan sulfate proteoglycan that shows a widespread distribution within the extracellular matrix of the brain. It plays an important role in the formation or maintenance of major neuronal structures in the brain. It also functions as a novel regulator to reduce the activity of matrix metalloproteinase (MMP) in adult T-cell leukemia (ATL). It suppresses membrane-type 1 MMP-mediated MMP-2 activation and tumor invasion. Moreover, TICN3 corresponding gene SPOCK3 acts as a risk gene for adult attention-deficit/hyperactivity disorder (ADHD) and personality disorders. TICN3 contains an N-terminal signal peptide, a testican-specific domain followed by the follistatin-like (FS) and extracellular calcium-binding (EC) domains characteristic of the BM-40 family. Towards the C-terminus they contain a thyroglobulin-like domain (TY) and a novel sequence (domain V), which includes two potential glycosaminoglycan attachment sites. The substitution of a ligating Asp residue by Tyr295 in the +Y position of EF-hand 2 in testican-3 could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ ion with low affinity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161076496 180 RTCSKSDRSQFNTNLMrmfrneaqsffrqPSLSDShiLEWQFSKLDTNGNKLLDRQEIRELkkVLRRNvkpRRCGRTFGK 259
Cdd:cd16239   31 KIVRRPERSRFDTSIL-------------PICKDS--LGWMFNRLDTNYDLLLDQSELGSI--YLDKN---EQCTKAFFN 90

                         90       100
                 ....*....|....*....|..
gi 161076496 260 YCDVTKDANLNWLEWSVCFTKE 281
Cdd:cd16239   91 SCDTYKDSLISNNEWCYCFQRQ 112

Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulphides.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 161076496   38 CDDNEG-PVCGTDGQTYPTRCHLLRAQCGGHQVS----LKYSGSC 77
Cdd:pfam07648   6 CPKTEYePVCGSDGVTYPSPCALCAAGCKLGKEVkeekVKYDGSC 50

EF-hand, extracellular calcium-binding (EC) motif, found in testican-2 (TICN2); TICN2, also termed SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 2 (Spock2), is an extracellular heparan sulphate proteoglycan expressed in brain, lung, and testis. It inhibits neurite extension from cultured primary cerebellar neurons and may play regulatory roles in the development of the central nervous system. It also participates in diverse steps of neurogenesis. Moreover, TICN2 may contribute to ECM remodeling by regulating function(s) of other testican family members, which possess membrane-type matrix metalloproteinases (MT-MMPs) inhibitory function. Furthermore, TICN2 corresponding gene SPOCK2 acts as a susceptibility gene for bronchopulmonary dysplasia. TICN2 contains an N-terminal signal peptide, a testican-specific domain followed by a follistatin-like (FS) domain, an extracellular calcium-binding (EC) domain including a pair of EF hands, a thyroglobulin-like domain (TY), and a C-terminal region with two putative glycosaminoglycan attachment sites. The substitution of a ligating Asp residue by Tyr292 in the +Y position of EF-hand 2 in TICN2 could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ ion with low affinity.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 161076496 219 WQFSKLDTNGNKLLDRQEIRELkkvlrrNV-KPRRCGRTFGKYCDVTKDANLNWLEWSVCFTKE 281
Cdd:cd16238   54 WMFSKLDTSGDLFLDQAELAAI------NLdKYEVCIRPFFNSCDTYRDGRVSTAEWCFCFWRE 111

Kazal-type pancreatic secretory trypsin inhibitors (PSTI) and related proteins, including the second domain of the ovomucoid turkey inhibitor and the C-terminal domain of the esophagus cancer-related gene-2 protein (ECRG-2), are members of the superfamily of kazal-type proteinase inhibitors and follistatin-like proteins.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 161076496  38 CDDNEGPVCGTDGQTYPTRCHL--LRAQCGGHqVSLKYSGSC 77
Cdd:cd01327    5 CPKDYDPVCGTDGVTYSNECLLcaENLKRQTN-IRIKHDGEC 45

EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein, acidic and rich in cysteine-like 1 (SPARCL1); SPARCL1, also termed SPARC-like protein 1, or high endothelial venule protein (Hevin), or MAST 9, or SC-1, or RAGS-1, or QR1, or ECM 2, is a diversely expressed and developmentally regulated extracellular matrix glycoprotein involved in tissue repair and remodeling via interaction with the surrounding extracellular matrix (ECM) proteins. It plays a pivotal role in the corneal wound healing. SPARCL1 may function as both a tumor suppressor and as a regulator of angiogenesis. It regulates cell migration/invasion and suppresses metastasis in many cancers, including prostate cancer, colorectal cancer, gastric cancer, and breast cancer. It can bind to collagens and be counter-adhesive to wild-type dermal fibroblasts, but do not influence rates of cell proliferation. Moreover, SPARCL1 contributes to neural development and participates in remodeling events associated with neuronal degeneration following neural injury. It can influence central nervous system (CNS) development and synaptic rearrangement. SPARCL1 is the closest family member to secreted protein acidic and rich in cysteine (SPARC), but does not compensate for the absence of SPARC in the CNS. SPARC contains an N-terminal acidic 52-residue segment followed by a follistatin-like (FS) domain, and an alpha-helical EC domain with 2 unusual calcium-binding EF-hands and the collagen-binding site. SPARCL1 shares the three primary domains contained within SPARC with an expanded N-terminal domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161076496 182 CSKSDRSQFNTNLMRMFRN-EAQSFFRQPslsdshiLEWQFSKLDTN-GNKLLDRQEIRELKKVLrrnVKPRRCGRTFGK 259
Cdd:cd16236    1 CTDSEVVQFPLRMRDWLKNiLMQLYYIYP-------VHWQFAQLDQHpSDRFLTHSELAPLRASL---VPMEHCITRFFQ 70

                         90
                 ....*....|....*....
gi 161076496 260 YCDVTKDANLNWLEWSVCF 278
Cdd:cd16236   71 ECDADKDKLITLKEWCHCF 89