HDDC2_HUMAN
ID HDDC2_HUMAN Reviewed; 204 AA.
AC Q7Z4H3; Q5TDQ4; Q6NZ49; Q9BTT2; Q9BV31; Q9Y3D1;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=5'-deoxynucleotidase HDDC2 {ECO:0000305};
DE EC=3.1.3.89 {ECO:0000250|UniProtKB:P53144};
DE AltName: Full=HD domain-containing protein 2;
DE AltName: Full=Hepatitis C virus NS5A-transactivated protein 2;
DE Short=HCV NS5A-transactivated protein 2;
GN Name=HDDC2; Synonyms=C6orf74, NS5ATP2; ORFNames=CGI-130;
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 [MRNA] (ISOFORM 1).
RC TISSUE=Hepatoma;
RX PubMed=15188496; DOI=10.3748/wjg.v10.i12.1735;
RA Yang Q., Cheng J., Liu Y., Hong Y., Wang J.-J., Zhang S.-L.;
RT "Cloning and identification of NS5ATP2 gene and its spliced variant
RT transactivated by hepatitis C virus non-structural protein 5A.";
RL World J. Gastroenterol. 10:1735-1739(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Brain, Lung, and Placenta;
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 [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3; SER-5 AND SER-204, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH MAGNESIUM.
RG Northeast structural genomics consortium (NESG);
RT "Northeast structural genomics consortium target HR6723.";
RL Submitted (APR-2012) to the PDB data bank.
CC -!- FUNCTION: Catalyzes the dephosphorylation of the nucleoside 5'-
CC monophosphates deoxyadenosine monophosphate (dAMP), deoxycytidine
CC monophosphate (dCMP), deoxyguanosine monophosphate (dGMP) and
CC deoxythymidine monophosphate (dTMP). {ECO:0000250|UniProtKB:P53144}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-phosphate + H2O = a 2'-
CC deoxyribonucleoside + phosphate; Xref=Rhea:RHEA:36167,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:18274, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:65317; EC=3.1.3.89;
CC Evidence={ECO:0000250|UniProtKB:P53144};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P53144};
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000250|UniProtKB:P53144};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P53144};
CC Note=Binds 2 divalent metal cations (Ref.9). Shows activity with
CC Mn(2+), Co(2+) and Mg(2+) but shows no activity with Zn(2+) (By
CC similarity). {ECO:0000250|UniProtKB:P53144, ECO:0000269|Ref.9};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P53144}.
CC -!- INTERACTION:
CC Q7Z4H3; Q9Y6K9: IKBKG; NbExp=3; IntAct=EBI-6163836, EBI-81279;
CC Q7Z4H3; P80188: LCN2; NbExp=3; IntAct=EBI-6163836, EBI-11911016;
CC Q7Z4H3; P01189: POMC; NbExp=3; IntAct=EBI-6163836, EBI-12219503;
CC Q7Z4H3; Q76353; Xeno; NbExp=2; IntAct=EBI-6163836, EBI-6248077;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q7Z4H3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7Z4H3-2; Sequence=VSP_029556;
CC Name=3;
CC IsoId=Q7Z4H3-3; Sequence=VSP_029557, VSP_029558;
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the HDDC2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD34125.1; Type=Miscellaneous discrepancy; Note=Correction of a non-canonical splice junction.; Evidence={ECO:0000305};
CC Sequence=AAH03357.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF529363; AAQ09597.1; -; mRNA.
DR EMBL; AF151888; AAD34125.1; ALT_SEQ; mRNA.
DR EMBL; AL121938; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW48138.1; -; Genomic_DNA.
DR EMBL; BC001671; AAH01671.1; -; mRNA.
DR EMBL; BC003357; AAH03357.2; ALT_INIT; mRNA.
DR EMBL; BC066332; AAH66332.1; -; mRNA.
DR CCDS; CCDS43503.1; -. [Q7Z4H3-1]
DR RefSeq; NP_057147.2; NM_016063.2. [Q7Z4H3-1]
DR PDB; 4DMB; X-ray; 1.90 A; A/B=1-204.
DR PDB; 4L1J; X-ray; 1.82 A; A/B=1-204.
DR PDB; 4L7E; X-ray; 2.23 A; A/B=1-204.
DR PDB; 4L7W; X-ray; 2.30 A; A=1-204.
DR PDBsum; 4DMB; -.
DR PDBsum; 4L1J; -.
DR PDBsum; 4L7E; -.
DR PDBsum; 4L7W; -.
DR AlphaFoldDB; Q7Z4H3; -.
DR SMR; Q7Z4H3; -.
DR BioGRID; 119226; 20.
DR IntAct; Q7Z4H3; 9.
DR MINT; Q7Z4H3; -.
DR STRING; 9606.ENSP00000381220; -.
DR GlyGen; Q7Z4H3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q7Z4H3; -.
DR PhosphoSitePlus; Q7Z4H3; -.
DR BioMuta; HDDC2; -.
DR DMDM; 74713511; -.
DR REPRODUCTION-2DPAGE; IPI00386751; -.
DR EPD; Q7Z4H3; -.
DR jPOST; Q7Z4H3; -.
DR MassIVE; Q7Z4H3; -.
DR MaxQB; Q7Z4H3; -.
DR PaxDb; Q7Z4H3; -.
DR PeptideAtlas; Q7Z4H3; -.
DR PRIDE; Q7Z4H3; -.
DR ProteomicsDB; 69179; -. [Q7Z4H3-1]
DR ProteomicsDB; 69180; -. [Q7Z4H3-2]
DR ProteomicsDB; 69181; -. [Q7Z4H3-3]
DR Antibodypedia; 32696; 58 antibodies from 19 providers.
DR DNASU; 51020; -.
DR Ensembl; ENST00000318787.13; ENSP00000316242.9; ENSG00000111906.18. [Q7Z4H3-3]
DR Ensembl; ENST00000398153.7; ENSP00000381220.1; ENSG00000111906.18. [Q7Z4H3-1]
DR Ensembl; ENST00000609477.5; ENSP00000476969.1; ENSG00000111906.18. [Q7Z4H3-3]
DR GeneID; 51020; -.
DR KEGG; hsa:51020; -.
DR MANE-Select; ENST00000398153.7; ENSP00000381220.1; NM_016063.3; NP_057147.2.
DR UCSC; uc003qaa.2; human. [Q7Z4H3-1]
DR CTD; 51020; -.
DR DisGeNET; 51020; -.
DR GeneCards; HDDC2; -.
DR HGNC; HGNC:21078; HDDC2.
DR HPA; ENSG00000111906; Low tissue specificity.
DR neXtProt; NX_Q7Z4H3; -.
DR OpenTargets; ENSG00000111906; -.
DR PharmGKB; PA134943525; -.
DR VEuPathDB; HostDB:ENSG00000111906; -.
DR eggNOG; KOG3197; Eukaryota.
DR GeneTree; ENSGT00390000009937; -.
DR HOGENOM; CLU_2739334_0_0_1; -.
DR InParanoid; Q7Z4H3; -.
DR OMA; YEKRDNI; -.
DR PhylomeDB; Q7Z4H3; -.
DR TreeFam; TF313855; -.
DR PathwayCommons; Q7Z4H3; -.
DR SignaLink; Q7Z4H3; -.
DR BioGRID-ORCS; 51020; 21 hits in 1076 CRISPR screens.
DR ChiTaRS; HDDC2; human.
DR GenomeRNAi; 51020; -.
DR Pharos; Q7Z4H3; Tdark.
DR PRO; PR:Q7Z4H3; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q7Z4H3; protein.
DR Bgee; ENSG00000111906; Expressed in pons and 214 other tissues.
DR ExpressionAtlas; Q7Z4H3; baseline and differential.
DR Genevisible; Q7Z4H3; HS.
DR GO; GO:0002953; F:5'-deoxynucleotidase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR006674; HD_domain.
DR InterPro; IPR039356; YfbR/HDDC2.
DR PANTHER; PTHR11845; PTHR11845; 1.
DR Pfam; PF13023; HD_3; 1.
DR SMART; SM00471; HDc; 1.
DR PROSITE; PS51831; HD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cobalt; Hydrolase;
KW Magnesium; Manganese; Metal-binding; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..204
FT /note="5'-deoxynucleotidase HDDC2"
FT /id="PRO_0000311389"
FT DOMAIN 46..148
FT /note="HD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01175"
FT BINDING 49
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:4DMB"
FT BINDING 77
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:4DMB"
FT BINDING 78
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:4DMB"
FT BINDING 81
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:4L7W"
FT BINDING 86
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:4L7W"
FT BINDING 87
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:4L7W"
FT BINDING 143
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:4DMB"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 3
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 5
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 204
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 70..103
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_029556"
FT VAR_SEQ 70..71
FT /note="CV -> KL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10810093,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_029557"
FT VAR_SEQ 72..204
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10810093,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_029558"
FT VARIANT 64
FT /note="R -> C (in dbSNP:rs12213371)"
FT /id="VAR_037238"
FT CONFLICT 69
FT /note="R -> P (in Ref. 2; AAD34125)"
FT /evidence="ECO:0000305"
FT CONFLICT 131
FT /note="Q -> R (in Ref. 5; AAH66332)"
FT /evidence="ECO:0000305"
FT HELIX 14..25
FT /evidence="ECO:0007829|PDB:4L1J"
FT HELIX 26..29
FT /evidence="ECO:0007829|PDB:4L1J"
FT HELIX 33..36
FT /evidence="ECO:0007829|PDB:4L1J"
FT TURN 37..39
FT /evidence="ECO:0007829|PDB:4L1J"
FT HELIX 46..59
FT /evidence="ECO:0007829|PDB:4L1J"
FT HELIX 67..76
FT /evidence="ECO:0007829|PDB:4L1J"
FT TURN 77..80
FT /evidence="ECO:0007829|PDB:4L1J"
FT HELIX 81..84
FT /evidence="ECO:0007829|PDB:4L1J"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:4L1J"
FT HELIX 95..110
FT /evidence="ECO:0007829|PDB:4L1J"
FT HELIX 115..130
FT /evidence="ECO:0007829|PDB:4L1J"
FT HELIX 134..158
FT /evidence="ECO:0007829|PDB:4L1J"
FT TURN 161..164
FT /evidence="ECO:0007829|PDB:4L1J"
FT HELIX 165..171
FT /evidence="ECO:0007829|PDB:4L1J"
FT HELIX 178..199
FT /evidence="ECO:0007829|PDB:4L1J"
SQ SEQUENCE 204 AA; 23390 MW; E59D03224F8D6A16 CRC64;
MASVSSATFS GHGARSLLQF LRLVGQLKRV PRTGWVYRNV QRPESVSDHM YRMAVMAMVI
KDDRLNKDRC VRLALVHDMA ECIVGDIAPA DNIPKEEKHR REEEAMKQIT QLLPEDLRKE
LYELWEEYET QSSAEAKFVK QLDQCEMILQ ASEYEDLEHK PGRLQDFYDS TAGKFNHPEI
VQLVSELEAE RSTNIAAAAS EPHS
