DDI1_HUMAN
ID DDI1_HUMAN Reviewed; 396 AA.
AC Q8WTU0; Q7Z4U6; Q8WTS3;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Protein DDI1 homolog 1;
DE EC=3.4.23.- {ECO:0000250|UniProtKB:I7HUG0};
GN Name=DDI1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Guo J.H., Yu L.;
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLY-142 AND GLU-239.
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=21266539; DOI=10.1096/fj.10-178947;
RA White R.E., Powell D.J., Berry C.;
RT "HIV proteinase inhibitors target the Ddi1-like protein of Leishmania
RT parasites.";
RL FASEB J. 25:1729-1736(2011).
RN [5]
RP FUNCTION.
RX PubMed=29290612; DOI=10.1016/j.molcel.2017.11.035;
RA Kottemann M.C., Conti B.A., Lach F.P., Smogorzewska A.;
RT "Removal of RTF2 from Stalled Replisomes Promotes Maintenance of Genome
RT Integrity.";
RL Mol. Cell 69:24-35.E5(2018).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 239-367.
RG Structural genomics consortium (SGC);
RT "Retropepsin-like domain of human DDI1.";
RL Submitted (JUL-2011) to the PDB data bank.
CC -!- FUNCTION: Probable aspartic protease (Probable). Seems to act as a
CC proteasomal shuttle which links the proteasome and replication fork
CC proteins like RTF2 (Probable). Required, with DDI2, for cellular
CC survival following replication stress. Together or redudantly with
CC DDI2, removes RTF2 from stalled forks to allow cell cycle progression
CC after replication stress and maintains genome integrity
CC (PubMed:29290612). {ECO:0000269|PubMed:29290612,
CC ECO:0000305|PubMed:21266539, ECO:0000305|PubMed:29290612}.
CC -!- ACTIVITY REGULATION: Inhibited by the proteinase inhibitors amprenavir,
CC indinavir, lopinavir, isovaleryl pepstatin, ritonavir and saquinavir.
CC {ECO:0000269|PubMed:21266539}.
CC -!- INTERACTION:
CC Q8WTU0; Q9NRJ3: CCL28; NbExp=10; IntAct=EBI-748248, EBI-7783254;
CC Q8WTU0; Q8WWM9: CYGB; NbExp=6; IntAct=EBI-748248, EBI-6309037;
CC Q8WTU0; O14645: DNALI1; NbExp=3; IntAct=EBI-748248, EBI-395638;
CC Q8WTU0; Q96MY7: FAM161B; NbExp=3; IntAct=EBI-748248, EBI-7225287;
CC Q8WTU0; O95872: GPANK1; NbExp=3; IntAct=EBI-748248, EBI-751540;
CC Q8WTU0; O14901: KLF11; NbExp=3; IntAct=EBI-748248, EBI-948266;
CC Q8WTU0; Q9P2K6: KLHL42; NbExp=8; IntAct=EBI-748248, EBI-739890;
CC Q8WTU0; Q6ZVX7: NCCRP1; NbExp=3; IntAct=EBI-748248, EBI-2877737;
CC Q8WTU0; P20618: PSMB1; NbExp=3; IntAct=EBI-748248, EBI-372273;
CC Q8WTU0; A0A087WYA8: RALGAPA2; NbExp=3; IntAct=EBI-748248, EBI-12847424;
CC Q8WTU0; Q9BUL9: RPP25; NbExp=3; IntAct=EBI-748248, EBI-366570;
CC Q8WTU0; P20132: SDS; NbExp=3; IntAct=EBI-748248, EBI-17859611;
CC Q8WTU0; Q9BXF9: TEKT3; NbExp=3; IntAct=EBI-748248, EBI-8644516;
CC Q8WTU0; Q12933: TRAF2; NbExp=3; IntAct=EBI-748248, EBI-355744;
CC Q8WTU0; P61086: UBE2K; NbExp=3; IntAct=EBI-748248, EBI-473850;
CC Q8WTU0; O75604: USP2; NbExp=3; IntAct=EBI-748248, EBI-743272;
CC -!- SIMILARITY: Belongs to the DDI1 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK093336; BAC04135.1; -; mRNA.
DR EMBL; AF429972; AAP97303.1; -; mRNA.
DR EMBL; BC021172; AAH21172.2; -; mRNA.
DR EMBL; BC021710; AAH21710.1; -; mRNA.
DR EMBL; BC022017; AAH22017.1; -; mRNA.
DR EMBL; BC022018; AAH22018.1; -; mRNA.
DR CCDS; CCDS31660.1; -.
DR RefSeq; NP_001001711.1; NM_001001711.2.
DR PDB; 3S8I; X-ray; 1.70 A; A/B=239-367.
DR PDBsum; 3S8I; -.
DR AlphaFoldDB; Q8WTU0; -.
DR SMR; Q8WTU0; -.
DR BioGRID; 136043; 37.
DR DIP; DIP-60626N; -.
DR IntAct; Q8WTU0; 31.
DR MINT; Q8WTU0; -.
DR STRING; 9606.ENSP00000302805; -.
DR MEROPS; A28.001; -.
DR iPTMnet; Q8WTU0; -.
DR PhosphoSitePlus; Q8WTU0; -.
DR BioMuta; DDI1; -.
DR DMDM; 74730631; -.
DR jPOST; Q8WTU0; -.
DR MassIVE; Q8WTU0; -.
DR MaxQB; Q8WTU0; -.
DR PaxDb; Q8WTU0; -.
DR PeptideAtlas; Q8WTU0; -.
DR PRIDE; Q8WTU0; -.
DR ProteomicsDB; 74599; -.
DR Antibodypedia; 31840; 65 antibodies from 21 providers.
DR DNASU; 414301; -.
DR Ensembl; ENST00000302259.5; ENSP00000302805.3; ENSG00000170967.5.
DR GeneID; 414301; -.
DR KEGG; hsa:414301; -.
DR MANE-Select; ENST00000302259.5; ENSP00000302805.3; NM_001001711.3; NP_001001711.1.
DR UCSC; uc001phr.3; human.
DR CTD; 414301; -.
DR DisGeNET; 414301; -.
DR GeneCards; DDI1; -.
DR HGNC; HGNC:18961; DDI1.
DR HPA; ENSG00000170967; Tissue enriched (testis).
DR neXtProt; NX_Q8WTU0; -.
DR OpenTargets; ENSG00000170967; -.
DR PharmGKB; PA142672003; -.
DR VEuPathDB; HostDB:ENSG00000170967; -.
DR eggNOG; KOG0012; Eukaryota.
DR GeneTree; ENSGT00950000182999; -.
DR HOGENOM; CLU_020435_1_0_1; -.
DR InParanoid; Q8WTU0; -.
DR OMA; EQPMDIL; -.
DR OrthoDB; 817208at2759; -.
DR PhylomeDB; Q8WTU0; -.
DR TreeFam; TF333421; -.
DR PathwayCommons; Q8WTU0; -.
DR SignaLink; Q8WTU0; -.
DR BioGRID-ORCS; 414301; 6 hits in 1066 CRISPR screens.
DR GenomeRNAi; 414301; -.
DR Pharos; Q8WTU0; Tbio.
DR PRO; PR:Q8WTU0; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q8WTU0; protein.
DR Bgee; ENSG00000170967; Expressed in sperm and 16 other tissues.
DR Genevisible; Q8WTU0; HS.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0072711; P:cellular response to hydroxyurea; IMP:UniProtKB.
DR GO; GO:0010498; P:proteasomal protein catabolic process; IMP:UniProtKB.
DR GO; GO:0097752; P:regulation of DNA stability; IMP:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; IMP:UniProtKB.
DR CDD; cd05479; RP_DDI; 1.
DR CDD; cd01796; Ubl_Ddi1_like; 1.
DR Gene3D; 2.40.70.10; -; 1.
DR InterPro; IPR033882; DDI1_N.
DR InterPro; IPR019103; Peptidase_aspartic_DDI1-type.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR Pfam; PF09668; Asp_protease; 1.
DR Pfam; PF00240; ubiquitin; 1.
DR SMART; SM00213; UBQ; 1.
DR SUPFAM; SSF50630; SSF50630; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aspartyl protease; Hydrolase; Protease; Reference proteome.
FT CHAIN 1..396
FT /note="Protein DDI1 homolog 1"
FT /id="PRO_0000287086"
FT DOMAIN 1..81
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT REGION 82..130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 374..396
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 100..126
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 376..396
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 260
FT /evidence="ECO:0000305"
FT VARIANT 136
FT /note="G -> S (in dbSNP:rs7102675)"
FT /id="VAR_032259"
FT VARIANT 142
FT /note="S -> G (in dbSNP:rs17856633)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_032260"
FT VARIANT 239
FT /note="G -> E (in dbSNP:rs17851870)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_032261"
FT CONFLICT 153
FT /note="N -> K (in Ref. 2; AAP97303)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="N -> K (in Ref. 2; AAP97303)"
FT /evidence="ECO:0000305"
FT CONFLICT 170
FT /note="A -> T (in Ref. 2; AAP97303)"
FT /evidence="ECO:0000305"
FT CONFLICT 213
FT /note="K -> R (in Ref. 2; AAP97303)"
FT /evidence="ECO:0000305"
FT STRAND 245..250
FT /evidence="ECO:0007829|PDB:3S8I"
FT STRAND 253..259
FT /evidence="ECO:0007829|PDB:3S8I"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:3S8I"
FT HELIX 270..275
FT /evidence="ECO:0007829|PDB:3S8I"
FT HELIX 279..281
FT /evidence="ECO:0007829|PDB:3S8I"
FT HELIX 284..286
FT /evidence="ECO:0007829|PDB:3S8I"
FT STRAND 297..309
FT /evidence="ECO:0007829|PDB:3S8I"
FT STRAND 312..321
FT /evidence="ECO:0007829|PDB:3S8I"
FT STRAND 325..330
FT /evidence="ECO:0007829|PDB:3S8I"
FT HELIX 332..337
FT /evidence="ECO:0007829|PDB:3S8I"
FT STRAND 341..343
FT /evidence="ECO:0007829|PDB:3S8I"
FT TURN 344..347
FT /evidence="ECO:0007829|PDB:3S8I"
FT STRAND 348..350
FT /evidence="ECO:0007829|PDB:3S8I"
FT TURN 352..354
FT /evidence="ECO:0007829|PDB:3S8I"
FT STRAND 357..359
FT /evidence="ECO:0007829|PDB:3S8I"
FT HELIX 363..365
FT /evidence="ECO:0007829|PDB:3S8I"
SQ SEQUENCE 396 AA; 44124 MW; 1127CBF7ED3C705D CRC64;
MLITVYCVRR DLSEVTFSLQ VSPDFELRNF KVLCEAESRV PVEEIQIIHM ERLLIEDHCS
LGSYGLKDGD IVVLLQKDNV GPRAPGRAPN QPRVDFSGIA VPGTSSSRPQ HPGQQQQRTP
AAQRSQGLAS GEKVAGLQGL GSPALIRSML LSNPHDLSLL KERNPPLAEA LLSGSLETFS
QVLMEQQREK ALREQERLRL YTADPLDREA QAKIEEEIRQ QNIEENMNIA IEEAPESFGQ
VTMLYINCKV NGHPLKAFVD SGAQMTIMSQ ACAERCNIMR LVDRRWAGVA KGVGTQRIIG
RVHLAQIQIE GDFLQCSFSI LEDQPMDMLL GLDMLRRHQC SIDLKKNVLV IGTTGTQTYF
LPEGELPLCS RMVSGQDESS DKEITHSVMD SGRKEH
