UniProtKB - O62305 (KCC2D_CAEEL)
Calcium/calmodulin-dependent protein kinase type II
unc-43
Functioni
Acts in the signaling of a variety of pathways and processes. Phosphorylates 'Ser-319' of daf-16 in response to stress signals, such as heat, starvation and oxidation, which plays a role in prolonging lifespan. Required for viability under chronic osmotic stress in which it acts downstream of osr-1. Has roles in locomotion, oocyte maturation, brood size, egg laying, defecation, meiotic maturation and neuronal cell fate specification. Required for the regulation of synaptic density and neuromuscular junction morphology. Regulates the synaptic trafficking of glr-1. Bidirectional modulator of neurotransmitter release with negative modulatory effects mainly mediated via slo-1 activation. Involved in activation of ADF neurons and increased tph-1 transcription following exposure to pathogenic bacteria which leads to learned olfactory aversion to the bacteria (PubMed:23325232, PubMed:23505381).
Implicated in the muscle regulation of spicule protraction. In conjunction with egl-2 has a role in the suppression of mating behavior under food deprivation to encourage foraging. Involved in restricting str-2 expression to only one of the two AWC neurons. May suppress the functional response to an internal pacemaker, perhaps by modulating the activity of the IP3 receptor.
15 PublicationsCatalytic activityi
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 41 | ATPPROSITE-ProRule annotation1 Publication | 1 | |
Active sitei | 134 | Proton acceptorCurated | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 18 – 26 | ATPPROSITE-ProRule annotationBy similarity | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- calmodulin binding Source: GO_Central
- calmodulin-dependent protein kinase activity Source: WormBase
- identical protein binding Source: IntAct
- metal ion binding Source: UniProtKB-KW
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine kinase activity Source: RHEA
- transmembrane transporter binding Source: WormBase
GO - Biological processi
- MAPK cascade Source: WormBase
- medium-term memory Source: WormBase
- peptidyl-serine phosphorylation Source: WormBase
- peptidyl-threonine phosphorylation Source: WormBase
- positive regulation of gene expression Source: UniProtKB
- protein phosphorylation Source: WormBase
- serotonin biosynthetic process Source: UniProtKB
Keywordsi
Molecular function | Calmodulin-binding, Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Stress response |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.11.17, 1045 |
Reactomei | R-CEL-3371571, HSF1-dependent transactivation R-CEL-4086398, Ca2+ pathway R-CEL-438066, Unblocking of NMDA receptors, glutamate binding and activation R-CEL-5578775, Ion homeostasis R-CEL-936837, Ion transport by P-type ATPases |
SignaLinki | O62305 |
Names & Taxonomyi
Protein namesi | Recommended name: Calcium/calmodulin-dependent protein kinase type II1 Publication (EC:2.7.11.17)Short name: CaM kinase II1 Publication Alternative name(s): Uncoordinated protein 43 |
Gene namesi | Name:unc-43 ORF Names:K11E8.1 |
Organismi | Caenorhabditis elegans |
Taxonomic identifieri | 6239 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Ecdysozoa › Nematoda › Chromadorea › Rhabditida › Rhabditina › Rhabditomorpha › Rhabditoidea › Rhabditidae › Peloderinae › Caenorhabditis |
Proteomesi |
|
Organism-specific databases
WormBasei | K11E8.1a ; CE42693 ; WBGene00006779 ; unc-43 K11E8.1b ; CE28052 ; WBGene00006779 ; unc-43 K11E8.1d ; CE28054 ; WBGene00006779 ; unc-43 K11E8.1e ; CE28055 ; WBGene00006779 ; unc-43 K11E8.1f ; CE28056 ; WBGene00006779 ; unc-43 K11E8.1g ; CE28057 ; WBGene00006779 ; unc-43 K11E8.1h ; CE28058 ; WBGene00006779 ; unc-43 K11E8.1i ; CE28059 ; WBGene00006779 ; unc-43 K11E8.1k ; CE28060 ; WBGene00006779 ; unc-43 K11E8.1l ; CE28061 ; WBGene00006779 ; unc-43 K11E8.1m ; CE35590 ; WBGene00006779 ; unc-43 K11E8.1n ; CE40979 ; WBGene00006779 ; unc-43 K11E8.1o ; CE41430 ; WBGene00006779 ; unc-43 K11E8.1p ; CE42670 ; WBGene00006779 ; unc-43 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Other locations
- axon 1 Publication
- Perikaryon 2 Publications
Note: Localizes at or near the Golgi apparatus (PubMed:16079277). Localizes to post-synaptic regions and is enriched in punctate structures in axons of AWC neurons where it co-localizes with tir-1. Localization is regulated by tir-1 (PubMed:15625192).2 Publications
Other locations
- axon cytoplasm Source: WormBase
- cytoplasm Source: GO_Central
- neuron projection Source: WormBase
- perikaryon Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cell projection, CytoplasmPathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 41 | K → M: Loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 97 | F → E: Loss of cooperative activation of adjacent holoenzyme subunits. 2 Publications | 1 | |
Mutagenesisi | 97 | F → K: Increase in calcium independent kinase activity, no effect on translocation to the neurite. 2 Publications | 1 | |
Mutagenesisi | 100 | I → K: Loss of cooperative activation of adjacent holoenzyme subunits. 1 Publication | 1 | |
Mutagenesisi | 108 | E → K in n498gf; slight increase in calcium independent kinase activity, no effect on translocation to the neurite. Nuclear translocation of daf-16 resulting in lifespan extension. 3 Publications | 1 | |
Mutagenesisi | 134 | D → N: Loss of autoinhibition and increase in binding of Ca2+/calmodulin. 2 Publications | 1 | |
Mutagenesisi | 147 | K → E: Slight increase in calcium independent kinase activity, no effect on translocation to the neurite. 1 Publication | 1 | |
Mutagenesisi | 170 | G → E in sy574; abnormal spicule protraction; when associated with V-665. 1 Publication | 1 | |
Mutagenesisi | 179 | S → L in e408; males display locomotor and muscle seizure defects and egg laying defects. 1 Publication | 1 | |
Mutagenesisi | 200 | I → K: Loss of cooperative activation of adjacent holoenzyme subunits. 1 Publication | 1 | |
Mutagenesisi | 236 | D → R: Increase in calcium independent kinase activity, loss of translocation to neurites and glr-1 trafficking. 1 Publication | 1 | |
Mutagenesisi | 278 – 279 | AI → DD: Decrease in binding of Ca2+/calmodulin. 1 Publication | 2 | |
Mutagenesisi | 280 | H → K: Increase in calcium independent kinase activity, no effect on translocation to the neurite. 1 Publication | 1 | |
Mutagenesisi | 281 | R → E: Increase in calcium independent kinase activity and translocation to an unlocalized pool in the neurite. Small decrease in glr-1 trafficking. 1 Publication | 1 | |
Mutagenesisi | 284 | T → D: Constitutively activate kinase activity, increase in translocation to the neurites. 1 Publication | 1 | |
Mutagenesisi | 665 | A → V in sy574; abnormal spicule protraction; when associated with E-170. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000396645 | 1 – 720 | Calcium/calmodulin-dependent protein kinase type IIAdd BLAST | 720 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 284 | Phosphothreonine; by autocatalysis1 Publication | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | O62305 |
PeptideAtlasi | O62305 |
PTM databases
iPTMneti | O62305 |
Expressioni
Tissue specificityi
Gene expression databases
ExpressionAtlasi | O62305, baseline and differential |
Interactioni
Subunit structurei
Dodecamer. Subunits are tightly packed around a central ring-shaped scaffold with extensive contacts between the regulatory segment of one kinase and the catalytic domain of another enabling cooperative activation of a subunit by the adjacent molecule (PubMed:16441656, PubMed:20139983).
Interacts with and phosphorylates daf-16; the interaction promotes daf-16 nuclear localization.
Interacts with egl-2 and tir-1 (PubMed:15625192, PubMed:21145946).
Interacts with nsy-1 (PubMed:11336672).
5 PublicationsBinary interactionsi
O62305
With | #Exp. | IntAct |
---|---|---|
syx-4 [P91409] | 3 | EBI-313095,EBI-326499 |
itself | 5 | EBI-313095,EBI-313095 |
GO - Molecular functioni
- calmodulin binding Source: GO_Central
- identical protein binding Source: IntAct
- transmembrane transporter binding Source: WormBase
Protein-protein interaction databases
BioGRIDi | 43023, 21 interactors |
DIPi | DIP-25971N DIP-58986N |
IntActi | O62305, 10 interactors |
MINTi | O62305 |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | O62305 |
SMRi | O62305 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O62305 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 12 – 269 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 258 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 317 – 345 | DisorderedSequence analysisAdd BLAST | 29 | |
Regioni | 504 – 586 | DisorderedSequence analysisAdd BLAST | 83 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 504 – 536 | Polar residuesSequence analysisAdd BLAST | 33 | |
Compositional biasi | 537 – 553 | Basic and acidic residuesSequence analysisAdd BLAST | 17 | |
Compositional biasi | 563 – 586 | Polar residuesSequence analysisAdd BLAST | 24 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0033, Eukaryota |
GeneTreei | ENSGT00940000159769 |
InParanoidi | O62305 |
OrthoDBi | 330091at2759 |
PhylomeDBi | O62305 |
Family and domain databases
InterProi | View protein in InterPro IPR013543, Ca/CaM-dep_prot_kinase-assoc IPR011009, Kinase-like_dom_sf IPR032710, NTF2-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF08332, CaMKII_AD, 1 hit PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF54427, SSF54427, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
s (15+)i Sequence
Sequence statusi: Complete.
This entry describes 15 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 15 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MMNASTKFSD NYDVKEELGK GAFSVVRRCV HKTTGLEFAA KIINTKKLSA
60 70 80 90 100
RDFQKLEREA RICRKLQHPN IVRLHDSIQE ESFHYLVFDL VTGGELFEDI
110 120 130 140 150
VAREFYSEAD ASHCIQQILE SIAYCHSNGI VHRDLKPENL LLASKAKGAA
160 170 180 190 200
VKLADFGLAI EVNDSEAWHG FAGTPGYLSP EVLKKDPYSK PVDIWACGVI
210 220 230 240 250
LYILLVGYPP FWDEDQHRLY AQIKAGAYDY PSPEWDTVTP EAKSLIDSML
260 270 280 290 300
TVNPKKRITA DQALKVPWIC NRERVASAIH RQDTVDCLKK FNARRKLKAA
310 320 330 340 350
ISAVKMVTRM SGVLRTSDST GSVASNGSTT HDASQVAGTS SQPTSPAAEV
360 370 380 390 400
YPNVLLFNPQ KFPRNCVHPF TTHPYYSPKE SSKKKLFFTL LFEVCPHTSR
410 420 430 440 450
SHILLRDNTK NIYHPYHCFT NKMSNYERAA PSSHGSSTTK KIANAIADLV
460 470 480 490 500
IRRSSPSIRR KTEADVHNSN RNRKVSAPAN LQHALVPVID VVVATGALAS
510 520 530 540 550
SSVDNLSAST SSDLGRNLLN KKEQGPPSTI KESSESSQTI DDNDSEKGGG
560 570 580 590 600
QLKHENTVVR ADGATGIVSS SNSSTASKSS STNLSAQKQD IVRVTQTLLD
610 620 630 640 650
AISCKDFETY TRLCDTSMTC FEPEALGNLI EGIEFHRFYF DGNRKNQVHT
660 670 680 690 700
TMLNPNVHII GEDAACVAYV KLTQFLDRNG EAHTRQSQES RVWSKKQGRW
710 720
VCVHVHRSTQ PSTNTTVSEF
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketG5EDZ5 | G5EDZ5_CAEEL | Calcium/calmodulin-dependent protei... | unc-43 CELE_K11E8.1, K11E8.1 | 681 | Annotation score: | ||
F5GUA8 | F5GUA8_CAEEL | CaMKII_AD domain-containing protein | unc-43 CELE_K11E8.1, K11E8.1 | 266 | Annotation score: | ||
F5GUA9 | F5GUA9_CAEEL | CaMKII_AD domain-containing protein | unc-43 CELE_K11E8.1, K11E8.1 | 298 | Annotation score: | ||
E7EM33 | E7EM33_CAEEL | CaMKII_AD domain-containing protein | unc-43 CELE_K11E8.1, K11E8.1 | 103 | Annotation score: |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_039590 | 1 – 505 | Missing in isoform n. 1 PublicationAdd BLAST | 505 | |
Alternative sequenceiVSP_039591 | 1 – 504 | Missing in isoform p. 1 PublicationAdd BLAST | 504 | |
Alternative sequenceiVSP_039592 | 1 – 490 | Missing in isoform a. 1 PublicationAdd BLAST | 490 | |
Alternative sequenceiVSP_039593 | 1 – 416 | Missing in isoform o. 1 PublicationAdd BLAST | 416 | |
Alternative sequenceiVSP_039594 | 1 – 414 | Missing in isoform m. 1 PublicationAdd BLAST | 414 | |
Alternative sequenceiVSP_039595 | 113 – 138 | HCIQQ…DLKPE → CCIMQILDGVNYCHQRGIVH RDMKV in isoform b. 1 PublicationAdd BLAST | 26 | |
Alternative sequenceiVSP_039596 | 139 – 720 | Missing in isoform b. 1 PublicationAdd BLAST | 582 | |
Alternative sequenceiVSP_039597 | 299 – 314 | AAISA…MSGVL → GAILTTMIATRNLSNL in isoform d, isoform g and isoform i. 3 PublicationsAdd BLAST | 16 | |
Alternative sequenceiVSP_039598 | 299 – 313 | AAISA…RMSGV → GAILTTMIATRNLSS in isoform f. 2 PublicationsAdd BLAST | 15 | |
Alternative sequenceiVSP_039599 | 299 – 302 | AAIS → VVDS in isoform k. 2 Publications | 4 | |
Alternative sequenceiVSP_039600 | 299 – 302 | AAIS → VAIC in isoform l. 2 Publications | 4 | |
Alternative sequenceiVSP_039601 | 303 – 720 | Missing in isoform k and isoform l. 2 PublicationsAdd BLAST | 418 | |
Alternative sequenceiVSP_039602 | 314 – 515 | Missing in isoform f. 2 PublicationsAdd BLAST | 202 | |
Alternative sequenceiVSP_039603 | 315 – 514 | Missing in isoform d, isoform g and isoform i. 3 PublicationsAdd BLAST | 200 | |
Alternative sequenceiVSP_039604 | 350 – 364 | VYPNV…QKFPR → GAILTTMIATRNLSN in isoform e and isoform h. 3 PublicationsAdd BLAST | 15 | |
Alternative sequenceiVSP_039605 | 365 – 513 | Missing in isoform e and isoform h. 3 PublicationsAdd BLAST | 149 | |
Alternative sequenceiVSP_039606 | 415 – 512 | PYHCF…ASTSS → MDGLLARLKLGSKRKKKTSS SVKRSSRPESARQAPRDTTG SLYSNLTASSSTVSACSAPE IVVLKKEQVVLAVDHKDQVD EQKKKNEQVVKKPEKLEVEA D in isoform m. 1 PublicationAdd BLAST | 98 | |
Alternative sequenceiVSP_039607 | 417 – 514 | HCFTN…TSSDL → MDGLLARLKLGSKRKKKTSS SVKRSSRPESARQAPRDTTG SLYSNLTASSSTVSACSAPE IVVLKKEQVVLAVDHKDQVD EQKKKNEQVVKKPEKLEVEA D in isoform o. 1 PublicationAdd BLAST | 98 | |
Alternative sequenceiVSP_039608 | 491 – 515 | VVVAT…SSDLG → MKNIEYWQVLLNKIFATYKI KMKQC in isoform a. 1 PublicationAdd BLAST | 25 | |
Alternative sequenceiVSP_039609 | 505 – 513 | NLSASTSSD → MIATRNLSN in isoform p. 1 Publication | 9 | |
Alternative sequenceiVSP_039610 | 506 – 515 | LSASTSSDLG → MNFLRFSGKC in isoform n. 1 Publication | 10 | |
Alternative sequenceiVSP_039611 | 548 – 585 | Missing in isoform d, isoform e and isoform o. 3 PublicationsAdd BLAST | 38 | |
Alternative sequenceiVSP_039612 | 549 – 550 | GG → NE in isoform i. 2 Publications | 2 | |
Alternative sequenceiVSP_039613 | 551 – 720 | Missing in isoform i. 2 PublicationsAdd BLAST | 170 |
Sequence databases
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2BDW | X-ray | 1.80 | A/B | 1-298 | [»] | |
A/B | 514-543 | [»] | ||||
2F86 | X-ray | 2.64 | B/D/F/H/J/L/N | 585-720 | [»] | |
3KK8 | X-ray | 1.72 | A | 5-288 | [»] | |
3KK9 | X-ray | 3.21 | A | 6-287 | [»] | |
3KL8 | X-ray | 3.37 | A/C/E/G/I | 5-273 | [»] | |
AlphaFoldDBi | O62305 | |||||
SMRi | O62305 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 43023, 21 interactors |
DIPi | DIP-25971N DIP-58986N |
IntActi | O62305, 10 interactors |
MINTi | O62305 |
PTM databases
iPTMneti | O62305 |
Proteomic databases
EPDi | O62305 |
PeptideAtlasi | O62305 |
Genome annotation databases
Organism-specific databases
CTDi | 177921 |
WormBasei | K11E8.1a ; CE42693 ; WBGene00006779 ; unc-43 K11E8.1b ; CE28052 ; WBGene00006779 ; unc-43 K11E8.1d ; CE28054 ; WBGene00006779 ; unc-43 K11E8.1e ; CE28055 ; WBGene00006779 ; unc-43 K11E8.1f ; CE28056 ; WBGene00006779 ; unc-43 K11E8.1g ; CE28057 ; WBGene00006779 ; unc-43 K11E8.1h ; CE28058 ; WBGene00006779 ; unc-43 K11E8.1i ; CE28059 ; WBGene00006779 ; unc-43 K11E8.1k ; CE28060 ; WBGene00006779 ; unc-43 K11E8.1l ; CE28061 ; WBGene00006779 ; unc-43 K11E8.1m ; CE35590 ; WBGene00006779 ; unc-43 K11E8.1n ; CE40979 ; WBGene00006779 ; unc-43 K11E8.1o ; CE41430 ; WBGene00006779 ; unc-43 K11E8.1p ; CE42670 ; WBGene00006779 ; unc-43 |
Phylogenomic databases
eggNOGi | KOG0033, Eukaryota |
GeneTreei | ENSGT00940000159769 |
InParanoidi | O62305 |
OrthoDBi | 330091at2759 |
PhylomeDBi | O62305 |
Enzyme and pathway databases
BRENDAi | 2.7.11.17, 1045 |
Reactomei | R-CEL-3371571, HSF1-dependent transactivation R-CEL-4086398, Ca2+ pathway R-CEL-438066, Unblocking of NMDA receptors, glutamate binding and activation R-CEL-5578775, Ion homeostasis R-CEL-936837, Ion transport by P-type ATPases |
SignaLinki | O62305 |
Miscellaneous databases
EvolutionaryTracei | O62305 |
PROi | PR:O62305 |
Gene expression databases
ExpressionAtlasi | O62305, baseline and differential |
Family and domain databases
InterProi | View protein in InterPro IPR013543, Ca/CaM-dep_prot_kinase-assoc IPR011009, Kinase-like_dom_sf IPR032710, NTF2-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF08332, CaMKII_AD, 1 hit PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF54427, SSF54427, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | KCC2D_CAEEL | |
Accessioni | O62305Primary (citable) accession number: O62305 Secondary accession number(s): A5JYT0 Q9U6Q0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 10, 2010 |
Last sequence update: | October 1, 2001 | |
Last modified: | May 25, 2022 | |
This is version 180 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Caenorhabditis annotation project |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Caenorhabditis elegans
Caenorhabditis elegans: entries, gene names and cross-references to WormBase - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families