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Protein

Replication protein A 70 kDa DNA-binding subunit

Gene

RPA1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates, that form during DNA replication or upon DNA stress. It prevents their reannealing and in parallel, recruits and activates different proteins and complexes involved in DNA metabolism (PubMed:27723720, PubMed:27723717). Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage (PubMed:9430682). In the cellular response to DNA damage, the RPA complex controls DNA repair and DNA damage checkpoint activation. Through recruitment of ATRIP activates the ATR kinase a master regulator of the DNA damage response (PubMed:24332808). It is required for the recruitment of the DNA double-strand break repair factors RAD51 and RAD52 to chromatin in response to DNA damage (PubMed:17765923). Also recruits to sites of DNA damage proteins like XPA and XPG that are involved in nucleotide excision repair and is required for this mechanism of DNA repair (PubMed:7697716). Plays also a role in base excision repair (BER) probably through interaction with UNG (PubMed:9765279). Also recruits SMARCAL1/HARP, which is involved in replication fork restart, to sites of DNA damage. May also play a role in telomere maintenance (PubMed:17959650). As part of the alternative replication protein A complex, aRPA, binds single-stranded DNA and probably plays a role in DNA repair. Compared to the RPA2-containing, canonical RPA complex, may not support chromosomal DNA replication and cell cycle progression through S-phase. The aRPA may not promote efficient priming by DNA polymerase alpha but could support DNA synthesis by polymerase delta in presence of PCNA and replication factor C (RFC), the dual incision/excision reaction of nucleotide excision repair and RAD51-dependent strand exchange (PubMed:19996105).12 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi197 – 281OBAdd BLAST85
Zinc fingeri481 – 503C4-typeSequence analysisAdd BLAST23

GO - Molecular functioni

  • damaged DNA binding Source: UniProtKB
  • G-rich strand telomeric DNA binding Source: BHF-UCL
  • metal ion binding Source: UniProtKB-KW
  • single-stranded DNA binding Source: UniProtKB

GO - Biological processi

  • base-excision repair Source: UniProtKB
  • DNA damage response, detection of DNA damage Source: Reactome
  • DNA-dependent DNA replication Source: ProtInc
  • DNA recombination Source: ProtInc
  • DNA repair Source: CACAO
  • DNA replication Source: UniProtKB
  • double-strand break repair via homologous recombination Source: UniProtKB
  • error-free translesion synthesis Source: Reactome
  • error-prone translesion synthesis Source: Reactome
  • G1/S transition of mitotic cell cycle Source: Reactome
  • interstrand cross-link repair Source: Reactome
  • mismatch repair Source: UniProtKB
  • nucleotide-excision repair Source: UniProtKB
  • nucleotide-excision repair, DNA gap filling Source: Reactome
  • nucleotide-excision repair, DNA incision Source: Reactome
  • nucleotide-excision repair, DNA incision, 3'-to lesion Source: Reactome
  • nucleotide-excision repair, DNA incision, 5'-to lesion Source: Reactome
  • nucleotide-excision repair, preincision complex assembly Source: Reactome
  • nucleotide-excision repair, preincision complex stabilization Source: Reactome
  • protein localization to chromosome Source: UniProtKB
  • regulation of cellular response to heat Source: Reactome
  • regulation of signal transduction by p53 class mediator Source: Reactome
  • telomere maintenance Source: UniProtKB
  • telomere maintenance via semi-conservative replication Source: Reactome
  • transcription-coupled nucleotide-excision repair Source: Reactome
  • translesion synthesis Source: Reactome

Keywordsi

Molecular functionDNA-binding
Biological processDNA damage, DNA recombination, DNA repair, DNA replication
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-110312. Translesion synthesis by REV1.
R-HSA-110314. Recognition of DNA damage by PCNA-containing replication complex.
R-HSA-110320. Translesion Synthesis by POLH.
R-HSA-174437. Removal of the Flap Intermediate from the C-strand.
R-HSA-176187. Activation of ATR in response to replication stress.
R-HSA-3108214. SUMOylation of DNA damage response and repair proteins.
R-HSA-3371453. Regulation of HSF1-mediated heat shock response.
R-HSA-3371511. HSF1 activation.
R-HSA-5358565. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
R-HSA-5358606. Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
R-HSA-5651801. PCNA-Dependent Long Patch Base Excision Repair.
R-HSA-5655862. Translesion synthesis by POLK.
R-HSA-5656121. Translesion synthesis by POLI.
R-HSA-5656169. Termination of translesion DNA synthesis.
R-HSA-5685938. HDR through Single Strand Annealing (SSA).
R-HSA-5685942. HDR through Homologous Recombination (HRR).
R-HSA-5693607. Processing of DNA double-strand break ends.
R-HSA-5693616. Presynaptic phase of homologous DNA pairing and strand exchange.
R-HSA-5696395. Formation of Incision Complex in GG-NER.
R-HSA-5696397. Gap-filling DNA repair synthesis and ligation in GG-NER.
R-HSA-5696400. Dual Incision in GG-NER.
R-HSA-6782135. Dual incision in TC-NER.
R-HSA-6782210. Gap-filling DNA repair synthesis and ligation in TC-NER.
R-HSA-6783310. Fanconi Anemia Pathway.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
R-HSA-68962. Activation of the pre-replicative complex.
R-HSA-69166. Removal of the Flap Intermediate.
R-HSA-69473. G2/M DNA damage checkpoint.
R-HSA-912446. Meiotic recombination.

Names & Taxonomyi

Protein namesi
Recommended name:
Replication protein A 70 kDa DNA-binding subunit
Short name:
RP-A p70
Alternative name(s):
Replication factor A protein 1
Short name:
RF-A protein 1
Single-stranded DNA-binding protein
Cleaved into the following chain:
Gene namesi
Name:RPA1
Synonyms:REPA1, RPA70
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000132383.11.
HGNCiHGNC:10289. RPA1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi41R → E: Loss of HELB-binding; when associated with E-43. 1 Publication1
Mutagenesisi43R → E: Loss of HELB-binding; when associated with E-41. 1 Publication1
Mutagenesisi449K → R: Significant reduction of sumoylation. Loss of sumoylation; when associated with R-577. 1 Publication1
Mutagenesisi500C → S: Loss of function in DNA replication and mismatch repair without effect on DNA-binding activity; when associated with S-503. 1 Publication1
Mutagenesisi503C → S: Loss of function in DNA replication and mismatch repair without effect on DNA-binding activity; when associated with S-500. 1 Publication1
Mutagenesisi577K → R: Slight sumoylation decrease. Loss of sumoylation; when associated with R-449. 1 Publication1

Organism-specific databases

DisGeNETi6117.
OpenTargetsiENSG00000132383.
PharmGKBiPA34651.

Chemistry databases

ChEMBLiCHEMBL1764940.

Polymorphism and mutation databases

BioMutaiRPA1.
DMDMi1350579.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004232311 – 616Replication protein A 70 kDa DNA-binding subunitAdd BLAST616
Initiator methionineiRemoved; alternate1 Publication
ChainiPRO_00000972602 – 616Replication protein A 70 kDa DNA-binding subunit, N-terminally processedAdd BLAST615

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Cross-linki22Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki88Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei163N6-acetyllysineCombined sources1
Cross-linki163Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei167N6-acetyllysineCombined sources1
Cross-linki167Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei180PhosphothreonineCombined sources1
Cross-linki183Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei191PhosphothreonineCombined sources1
Cross-linki220Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki244Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei259N6-acetyllysineCombined sources1
Cross-linki259Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki267Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki331Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei384PhosphoserineCombined sources1
Cross-linki410Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki431Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki449Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Cross-linki458Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki553Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki577Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication

Post-translational modificationi

DNA damage-induced 'Lys-63'-linked polyubiquitination by PRPF19 mediates ATRIP recruitment to the RPA complex at sites of DNA damage and activation of ATR (PubMed:24332808). Ubiquitinated by RFWD3 at stalled replication forks in response to DNA damage: ubiquitination by RFWD3 does not lead to degradation by the proteasome and promotes removal of the RPA complex from stalled replication forks, promoting homologous recombination (PubMed:26474068).2 Publications
Sumoylated on lysine residues Lys-449 and Lys-577, with Lys-449 being the major site. Sumoylation promotes recruitment of RAD51 to the DNA damage foci to initiate DNA repair through homologous recombination. Desumoylated by SENP6.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP27694.
MaxQBiP27694.
PaxDbiP27694.
PeptideAtlasiP27694.
PRIDEiP27694.

PTM databases

iPTMnetiP27694.
PhosphoSitePlusiP27694.
SwissPalmiP27694.

Expressioni

Gene expression databases

BgeeiENSG00000132383.
CleanExiHS_RPA1.
ExpressionAtlasiP27694. baseline and differential.
GenevisibleiP27694. HS.

Organism-specific databases

HPAiCAB004563.
HPA006914.
HPA046497.

Interactioni

Subunit structurei

Component of the canonical replication protein A complex (RPA), an heterotrimer composed of RPA1, RPA2 and RPA3 (PubMed:27723720, PubMed:27723717). Also component of the aRPA, the alternative replication protein A complex, a trimeric complex similar to the replication protein A complex/RPA but where RPA1 and RPA3 are associated with RPA4 instead of RPA2 (PubMed:7760808, PubMed:19116208). The DNA-binding activity may reside exclusively on the RPA1 subunit. Interacts with PRPF19; the PRP19-CDC5L complex is recruited to the sites of DNA repair where it ubiquitinates the replication protein A complex (RPA) (PubMed:24332808). Interacts with RIPK1 (PubMed:16135809). Interacts with the polymerase alpha subunit POLA1/p180; this interaction stabilizes the replicative complex and reduces the misincorporation rate of DNA polymerase alpha by acting as a fidelity clamp (PubMed:9214288). Interacts with RAD51 and SENP6 to regulate DNA repair (PubMed:20705237). Interacts with HELB; this interaction promotes HELB recruitment to chromatin following DNA damage (PubMed:22194613, PubMed:26774285). Interacts with PRIMPOL (PubMed:24126761). Interacts with XPA; the interaction is direct and associates XPA with the RPA complex (PubMed:7700386, PubMed:9699634, PubMed:10563794). Interacts with ETAA1; the interaction is direct and promotes ETAA1 recruitment at stalled replication forks (PubMed:27601467, PubMed:27723720, PubMed:27723717).15 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi112037. 475 interactors.
CORUMiP27694.
DIPiDIP-24189N.
IntActiP27694. 68 interactors.
MINTiMINT-91488.
STRINGi9606.ENSP00000254719.

Chemistry databases

BindingDBiP27694.

Structurei

Secondary structure

1616
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi2 – 4Combined sources3
Helixi9 – 14Combined sources6
Turni15 – 17Combined sources3
Beta strandi18 – 20Combined sources3
Beta strandi24 – 32Combined sources9
Beta strandi36 – 38Combined sources3
Beta strandi42 – 47Combined sources6
Beta strandi49 – 58Combined sources10
Helixi60 – 62Combined sources3
Helixi63 – 67Combined sources5
Beta strandi70 – 74Combined sources5
Beta strandi76 – 86Combined sources11
Beta strandi88 – 90Combined sources3
Beta strandi92 – 103Combined sources12
Helixi105 – 108Combined sources4
Helixi187 – 189Combined sources3
Beta strandi198 – 206Combined sources9
Beta strandi210 – 213Combined sources4
Beta strandi218 – 227Combined sources10
Beta strandi232 – 238Combined sources7
Helixi239 – 245Combined sources7
Helixi246 – 248Combined sources3
Beta strandi254 – 258Combined sources5
Beta strandi261 – 264Combined sources4
Helixi267 – 269Combined sources3
Beta strandi275 – 279Combined sources5
Beta strandi285 – 288Combined sources4
Helixi305 – 310Combined sources6
Beta strandi316 – 326Combined sources11
Beta strandi330 – 334Combined sources5
Turni335 – 338Combined sources4
Beta strandi339 – 349Combined sources11
Beta strandi355 – 361Combined sources7
Helixi362 – 367Combined sources6
Beta strandi375 – 384Combined sources10
Beta strandi388 – 392Combined sources5
Beta strandi398 – 402Combined sources5
Helixi406 – 416Combined sources11
Turni417 – 419Combined sources3
Helixi445 – 451Combined sources7
Turni452 – 454Combined sources3
Beta strandi455 – 458Combined sources4
Beta strandi460 – 471Combined sources12
Beta strandi477 – 480Combined sources4
Beta strandi491 – 493Combined sources3
Turni494 – 496Combined sources3
Beta strandi497 – 500Combined sources4
Turni501 – 504Combined sources4
Beta strandi505 – 509Combined sources5
Beta strandi512 – 521Combined sources10
Beta strandi526 – 532Combined sources7
Helixi533 – 540Combined sources8
Helixi544 – 550Combined sources7
Helixi555 – 564Combined sources10
Turni565 – 567Combined sources3
Beta strandi569 – 577Combined sources9
Beta strandi588 – 596Combined sources9
Helixi599 – 615Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EWINMR-A1-114[»]
1FGUX-ray2.50A/B182-432[»]
1JMCX-ray2.40A181-422[»]
1L1OX-ray2.80C/F436-616[»]
2B29X-ray1.60A1-120[»]
2B3GX-ray1.60A1-120[»]
4IJHX-ray1.50A1-120[»]
4IJLX-ray1.70A1-120[»]
4IPCX-ray1.22A1-120[»]
4IPDX-ray1.51A1-120[»]
4IPGX-ray1.58A1-120[»]
4IPHX-ray1.94A1-120[»]
4LUOX-ray1.54A1-120[»]
4LUVX-ray1.40A1-120[»]
4LUZX-ray1.90A1-120[»]
4LW1X-ray1.63A1-120[»]
4LWCX-ray1.61A1-120[»]
4NB3X-ray1.35A/B1-120[»]
4O0AX-ray1.20A1-120[»]
4R4CX-ray1.40A1-120[»]
4R4IX-ray1.40A1-120[»]
4R4OX-ray1.33A1-120[»]
4R4QX-ray1.35A1-120[»]
4R4TX-ray1.28A1-120[»]
5E7NX-ray1.21A1-120[»]
5EAYX-ray1.55A/B/C/D3-120[»]
5N85X-ray2.00A1-120[»]
5N8AX-ray1.28A1-120[»]
DisProtiDP00061.
ProteinModelPortaliP27694.
SMRiP27694.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27694.

Family & Domainsi

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri481 – 503C4-typeSequence analysisAdd BLAST23

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0851. Eukaryota.
COG1599. LUCA.
GeneTreeiENSGT00390000012403.
HOGENOMiHOG000162322.
HOVERGENiHBG010502.
InParanoidiP27694.
KOiK07466.
OMAiDMTRNKL.
OrthoDBiEOG091G02VJ.
PhylomeDBiP27694.
TreeFamiTF105241.

Family and domain databases

CDDicd04476. RPA1_DBD_C. 1 hit.
cd04477. RPA1N. 1 hit.
InterProiView protein in InterPro
IPR012340. NA-bd_OB-fold.
IPR004365. NA-bd_OB_tRNA.
IPR013955. Rep_factor-A_C.
IPR007199. Rep_factor-A_N.
IPR031657. REPA_OB_2.
IPR004591. Rfa1.
PfamiView protein in Pfam
PF04057. Rep-A_N. 1 hit.
PF08646. Rep_fac-A_C. 1 hit.
PF16900. REPA_OB_2. 1 hit.
PF01336. tRNA_anti-codon. 1 hit.
SUPFAMiSSF50249. SSF50249. 4 hits.
TIGRFAMsiTIGR00617. rpa1. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P27694-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVGQLSEGAI AAIMQKGDTN IKPILQVINI RPITTGNSPP RYRLLMSDGL
60 70 80 90 100
NTLSSFMLAT QLNPLVEEEQ LSSNCVCQIH RFIVNTLKDG RRVVILMELE
110 120 130 140 150
VLKSAEAVGV KIGNPVPYNE GLGQPQVAPP APAASPAASS RPQPQNGSSG
160 170 180 190 200
MGSTVSKAYG ASKTFGKAAG PSLSHTSGGT QSKVVPIASL TPYQSKWTIC
210 220 230 240 250
ARVTNKSQIR TWSNSRGEGK LFSLELVDES GEIRATAFNE QVDKFFPLIE
260 270 280 290 300
VNKVYYFSKG TLKIANKQFT AVKNDYEMTF NNETSVMPCE DDHHLPTVQF
310 320 330 340 350
DFTGIDDLEN KSKDSLVDII GICKSYEDAT KITVRSNNRE VAKRNIYLMD
360 370 380 390 400
TSGKVVTATL WGEDADKFDG SRQPVLAIKG ARVSDFGGRS LSVLSSSTII
410 420 430 440 450
ANPDIPEAYK LRGWFDAEGQ ALDGVSISDL KSGGVGGSNT NWKTLYEVKS
460 470 480 490 500
ENLGQGDKPD YFSSVATVVY LRKENCMYQA CPTQDCNKKV IDQQNGLYRC
510 520 530 540 550
EKCDTEFPNF KYRMILSVNI ADFQENQWVT CFQESAEAIL GQNAAYLGEL
560 570 580 590 600
KDKNEQAFEE VFQNANFRSF IFRVRVKVET YNDESRIKAT VMDVKPVDYR
610
EYGRRLVMSI RRSALM
Length:616
Mass (Da):68,138
Last modified:February 1, 1996 - v2
Checksum:iFE038F40F5886CD1
GO

Sequence cautioni

P27694: The sequence BAD92969 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019236351T → A2 PublicationsCorresponds to variant dbSNP:rs5030755Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M63488 mRNA. Translation: AAA36584.1.
AK289704 mRNA. Translation: BAF82393.1.
AB209732 mRNA. Translation: BAD92969.1. Different initiation.
AY599563 Genomic DNA. Translation: AAS94324.1.
CH471108 Genomic DNA. Translation: EAW90574.1.
BC018126 mRNA. Translation: AAH18126.1.
CCDSiCCDS11014.1.
PIRiA40457.
RefSeqiNP_002936.1. NM_002945.3.
UniGeneiHs.461925.

Genome annotation databases

EnsembliENST00000254719; ENSP00000254719; ENSG00000132383.
GeneIDi6117.
KEGGihsa:6117.
UCSCiuc002fto.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiRFA1_HUMAN
AccessioniPrimary (citable) accession number: P27694
Secondary accession number(s): A8K0Y9, Q59ES9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: February 1, 1996
Last modified: October 25, 2017
This is version 191 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families