IGc2

Immunoglobulin C-2 Type

• SMART accession number: SM00408
• Interpro abstract (IPR003598):

  The basic structure of immunoglobulin (Ig) molecules is a tetramer of two light chains and two heavy chains linked by disulphide bonds. There are two types of light chains: kappa and lambda, each composed of a constant domain (CL) and a variable domain (VL). There are five types of heavy chains: alpha, delta, epsilon, gamma and mu, all consisting of a variable domain (VH) and three (in alpha, delta and gamma) or four (in epsilon and mu) constant domains (CH1 to CH4). Ig molecules are highly modular proteins, in which the variable and constant domains have clear, conserved sequence patterns. The domains in Ig and Ig-like molecules are grouped into four types: V-set (variable; IPR013106), C1-set (constant-1; IPR003597), C2-set (constant-2; IPR008424) and I-set (intermediate; IPR013098) [(PUBMED:9417933)]. Structural studies have shown that these domains share a common core Greek-key beta-sandwich structure, with the types differing in the number of strands in the beta-sheets as well as in their sequence patterns [(PUBMED:15327963), (PUBMED:11377196)].

  Immunoglobulin-like domains that are related in both sequence and structure can be found in several diverse protein families. Ig-like domains are involved in a variety of functions, including cell-cell recognition, cell-surface receptors, muscle structure and the immune system [(PUBMED:10698639)].

  This entry represents a subtype of the immunoglobulin domain, and is found in a diverse range of protein families that includes glycoproteins, fibroblast growth factor receptors, vascular endothelial growth factor receptors, interleukin-6 receptor, and neural cell adhesion molecules. It also includes proteins that are classified as unassigned proteinase inhibitors belonging to MEROPS inhibitor families I2, I17 and I43 [(PUBMED:14705960)].

There are 26595 IGc2 domains in 10384 proteins in SMART's nrdb database.

Disease (disease genes where sequence variants are found in this domain)

SwissProt sequences and OMIM curated human diseases associated with missense mutations within the IGc2 domain.

Protein	Disease
Fibroblast growth factor receptor 2 (P21802) (SMART)	OMIM:176943: Crouzon syndrome OMIM:123500: Jackson-Weiss syndrome OMIM:123150: Beare-Stevenson cutis gyrata syndrome OMIM:123790: Pfeiffer syndrome OMIM:101600: Apert syndrome OMIM:101200: Saethre-Chotzen syndrome
Netrin receptor DCC (P43146) (SMART)	OMIM:120470: Colorectal cancer
Myosin-binding protein C, cardiac-type (Q14896) (SMART)	OMIM:600958: Cardiomyopathy, familial hypertrophic, 4 OMIM:115197:
Low affinity immunoglobulin gamma Fc region receptor II-a (P12318) (SMART)	OMIM:146790: {Lupus nephritis, susceptibility to}
Low affinity immunoglobulin gamma Fc region receptor III-A (P08637) (SMART)	OMIM:146740: {Lupus erythematosus, systemic, susceptibility} OMIM:152700: Neutropenia, alloimmune neonatal ; {Viral infections, recurrent}
Neural cell adhesion molecule L1 (P32004) (SMART)	OMIM:308840: Hydrocephalus due to aqueductal stenosis OMIM:307000: MASA syndrome OMIM:303350: Spastic paraplegia OMIM:312900:

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
19.92	map04514	Cell adhesion molecules (CAMs)
9.21	map04060	Cytokine-cytokine receptor interaction
7.59	map04360	Axon guidance
7.18	map04810	Regulation of actin cytoskeleton
6.23	map04640	Hematopoietic cell lineage
6.10	map04510	Focal adhesion
4.88	map04670	Leukocyte transendothelial migration
3.79	map05215	Prostate cancer
2.98	map04520	Adherens junction
2.85	map04662	B cell receptor signaling pathway
2.85	map04660	T cell receptor signaling pathway
2.57	map05120	Epithelial cell signaling in Helicobacter pylori infection
2.57	map04020	Calcium signaling pathway
2.57	map04010	MAPK signaling pathway
2.57	map05218	Melanoma
1.90	map05210	Colorectal cancer
1.22	map04370	VEGF signaling pathway
1.22	map05214	Glioma
1.22	map04540	Gap junction
1.08	map05219	Bladder cancer
1.08	map04012	ErbB signaling pathway
0.95	map04916	Melanogenesis
0.95	map04530	Tight junction
0.95	map04620	Toll-like receptor signaling pathway
0.95	map04940	Type I diabetes mellitus
0.95	map05221	Acute myeloid leukemia
0.81	map04910	Insulin signaling pathway
0.54	map00940	Phenylpropanoid biosynthesis
0.54	map04512	ECM-receptor interaction
0.54	map00680	Methane metabolism
0.54	map04664	Fc epsilon RI signaling pathway
0.54	map00360	Phenylalanine metabolism
0.14	map04650	Natural killer cell mediated cytotoxicity

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with IGc2 domain which could be assigned to a KEGG orthologous group, and not all proteins containing IGc2 domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of IGc2 domains in PDB

PDB code	Title
1bih	Crystal structure of the insect immune protein hemolin: a new domain arrangement with implications for homophilic adhesion
1cs6	N-terminal fragment of axonin-1 from chicken
1cvs	Crystal structure of a dimeric fgf2-fgfr1 complex
1djs	Ligand-binding portion of fibroblast growth factor receptor in complex with fgf1
1e07	Model of human carcinoembryonic antigen by homology modelling and curve-fitting to experimental solution scattering data
1e0o	Crystal structure of a ternary fgf1-fgfr2-heparin complex
1epf	Crystal structure of the two n-terminal immunoglobulin domains of the neural cell adhesion molecule (ncam)
1ev2	Crystal structure of fgf2 in complex with the extracellular ligand binding domain of fgf receptor 2 (fgfr2)
1evt	Crystal structure of fgf1 in complex with the extracellular ligand binding domain of fgf receptor 1 (fgfr1)
1f2q	Crystal structure of the human high-affinity ige receptor
1f42	The p40 domain of human interleukin-12
1f45	Human interleukin-12
1f6a	Structure of the human ige-fc bound to its high affinity receptor fc(epsilon)ri(alpha)
1fhg	High resolution refinement of telokin
1fq9	Crystal structure of a ternary fgf2-fgfr1-heparin complex
1gl4	Nidogen-1 g2/perlecan ig3 complex
1h5b	T cell receptor valpha11 (av11s5) domain
1ie5	Nmr structure of the third immunoglobulin domain from the neural cell adhesion molecule.
1ii4	Crystal structure of ser252trp apert mutant fgf receptor 2 (fgfr2) in complex with fgf2
1iil	Crystal structure of pro253arg apert mutant fgf receptor 2 (fgfr2) in complex with fgf2
1j86	Human high affinity fc receptor fc(epsilon)ri(alpha), monoclinic crystal form 2
1j87	Human high affinity fc receptor fc(epsilon)ri(alpha), hexagonal crystal form 1
1j88	Human high affinity fc receptor fc(epsilon)ri(alpha), tetragonal crystal form 1
1j89	Human high affinity fc receptor fc(epsilon)ri(alpha), tetragonal crystal form 2
1jbj	Cd3 epsilon and gamma ectodomain fragment complex in single- chain construct
1koa	Twitchin kinase fragment (c.elegans), autoregulated protein kinase and immunoglobulin domains
1l6z	Crystal structure of murine ceacam1a[1,4]: a coronavirus receptor and cell adhesion molecule in the cea family
1n26	Crystal structure of the extra-cellular domains of human interleukin-6 receptor alpha chain
1nct	Titin module m5, n-terminally extended, nmr
1ncu	Titin module m5, n-terminally extended, nmr
1nun	Crystal structure analysis of the fgf10-fgfr2b complex
1qz1	Crystal structure of the ig 1-2-3 fragment of ncam
1rhf	Crystal structure of human tyro3-d1d2
1rpq	High affinity ige receptor (alpha chain) complexed with tight-binding e131 'zeta' peptide from phage display
1ry7	Crystal structure of the 3 ig form of fgfr3c in complex with fgf1
1sy6	Crystal structure of cd3gammaepsilon heterodimer in complex with okt3 fab fragment
1tlk	X-ray structure determination of telokin, the c-terminal domain of myosin light chain kinase, at 2.8 angstroms resolution
1tnm	Tertiary structure of an immunoglobulin-like domain from the giant muscle protein titin: a new member of the i set
1tnn	Tertiary structure of an immunoglobulin-like domain from the giant muscle protein titin: a new member of the i set
1u2h	X-ray structure of the n-terminally truncated human apep-1
1wvz	Solution structure of the d2 domain of the fibroblast growth factor
1xiw	Crystal structure of human cd3-e/d dimer in complex with a ucht1 single-chain antibody fragment
1xmw	Cd3 epsilon and delta ectodomain fragment complex in single- chain construct
1ya5	Crystal structure of the titin domains z1z2 in complex with telethonin
2a38	Crystal structure of the n-terminus of titin
2ckn	Nmr structure of the first ig module of mouse fgfr1
2cpc	Solution structure of rsgi ruh-030, an ig like domain from human cdna
2cr3	Solution structure of the first ig-like domain of human fibroblast growth factor receptor 1
2d3v	Crystal structure of leukocyte ig-like receptor a5 (lilra5/lir9/ilt11)
2dl9	Solution structure of the ig-like domain of human leucine- rich repeat-containing protein 4
2dm2	Solution structure of the first ig domain of human palladin
2dm3	Solution structure of the second ig domain of human palladin
2dm7	Solution structure of the 14th ig-like domain of human kiaa1556 protein
2e9w	Crystal structure of the extracellular domain of kit in complex with stem cell factor (scf)
2ec8	Crystal structure of the exctracellular domain of the receptor tyrosine kinase, kit
2edf	Solution structure of the second ig-like domain(2826-2915) from human obscurin
2edj	Solution structure of the fifth ig-like domain from human roundabout homolog 2
2edl	Solution structure of the ig-like domain (3801-3897) of human obscurin
2edw	Solution structure of the i-set domain (3537-3630) of human obscurin
2ens	Solution structure of the third ig-like domain from human advanced glycosylation end product-specific receptor
2eo9	Solution structure of the fifth ig-like domain from human roundabout homo1
2f8v	Structure of full length telethonin in complex with the n- terminus of titin
2fdb	Crystal structure of fibroblast growth factor (fgf)8b in complex with fgf receptor (fgfr) 2c
2id5	Crystal structure of the lingo-1 ectodomain
2iep	Crystal structure of immunoglobulin-like domains 1 and 2 of the receptor tyrosine kinase musk
2jlk	Crystal structure of ncam2 igiv-fn3i
2jll	Crystal structure of ncam2 igiv-fn3ii
2kkq	Solution nmr structure of the ig-like c2-type 2 domain of human myotilin. northeast structural genomics target hr3158.
2ncm	Neural cell adhesion molecule, nmr, 20 structures
2npl	Nmr structure of card d2 domain
2o26	Structure of a class iii rtk signaling assembly
2om5	N-terminal fragment of human tax1
2r15	Crystal structure of the myomesin domains 12 and 13
2rik	I-band fragment i67-i69 from titin
2rjm	3ig structure of titin domains i67-i69 e-to-a mutated variant
2v44	Crystal structure of ncam2 ig1-2
2v5m	Structural basis for dscam isoform specificity
2v5r	Structural basis for dscam isoform specificity
2v5s	Structural basis for dscam isoform specificity
2v5t	Crystal structure of ncam2 ig2-3
2v9q	First and second ig domains from human robo1
2v9r	First and second ig domains from human robo1 (form 2)
2v9t	Complex between the second lrr domain of slit2 and the first ig domain from robo1
2va4	Crystal structure of ncam2 ig34
2vaj	Crystal structure of ncam2 ig1 (i4122 cell unit)
2vr9	Drosophila robo ig1-2 (tetragonal form)
2vra	Drosophila robo ig1-2 (monoclinic form)
2yr3	Solution structure of the fourth ig-like domain from myosin light chain kinase, smooth muscle
3b43	I-band fragment i65-i70 from titin
3caf	Crystal structure of hfgfr2 d2 domain
3cu1	Crystal structure of 2:2:2 fgfr2d2:fgf1:sos complex
3d85	Crystal structure of il-23 in complex with neutralizing fab
3d87	Crystal structure of interleukin-23
3dar	Crystal structure of d2 domain from human fgfr2
3dmk	Crystal structure of down syndrome cell adhesion molecule (dscam) isoform 1.30.30, n-terminal eight ig domains
3duh	Structure of interleukin-23
3ejj	Structure of m-csf bound to the first three domains of fms
3euu	Crystal structure of the fgfr2 d2 domain
3grw	Fgfr3 in complex with a fab
3irg	High resolution structure of human titin in complex with obscurin like 1
3k0w	Crystal structure of the tandem ig-like c2-type 2 domains of the human mucosa-associated lymphoid tissue lymphoma translocation protein 1
3ncm	Neural cell adhesion molecule, module 2, nmr, 20 structures

Links (links to other resources describing this domain)

• PFAM: ig
• INTERPRO: IPR003598