ID   HAGHL_HUMAN             Reviewed;         290 AA.
AC   Q6PII5; A6NCC4; D3DU64; Q59FX8; Q96BZ3; Q96NR5; Q96S11; Q9BT45;
DT   15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   24-JAN-2024, entry version 139.
DE   RecName: Full=Hydroxyacylglutathione hydrolase-like protein;
DE            EC=3.1.2.-;
GN   Name=HAGHL;
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] (ISOFORM 3).
RC   TISSUE=Cerebellum;
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 GENOMIC DNA].
RX   PubMed=11157797; DOI=10.1093/hmg/10.4.339;
RA   Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C.,
RA   Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R.;
RT   "Sequence, structure and pathology of the fully annotated terminal 2 Mb of
RT   the short arm of human chromosome 16.";
RL   Hum. Mol. Genet. 10:339-352(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15616553; DOI=10.1038/nature03187;
RA   Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA   Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA   Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA   Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA   Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA   Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA   Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA   Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA   Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA   Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA   Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA   Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA   Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA   Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA   Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA   Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA   Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA   Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA   Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA   DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA   Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA   Myers R.M., Rubin E.M., Pennacchio L.A.;
RT   "The sequence and analysis of duplication-rich human chromosome 16.";
RL   Nature 432:988-994(2004).
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 4).
RC   TISSUE=Brain, Eye, and Skin;
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   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-191.
RC   TISSUE=Brain;
RA   Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA   Ohara O., Nagase T., Kikuno R.F.;
RL   Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Hydrolase acting on ester bonds. {ECO:0000305}.
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250};
CC   -!- INTERACTION:
CC       Q6PII5; Q0VDC6: FKBP1A; NbExp=3; IntAct=EBI-6255752, EBI-10226858;
CC       Q6PII5; D3DTS7: PMP22; NbExp=3; IntAct=EBI-6255752, EBI-25882629;
CC       Q6PII5; Q8NE91: TM4SF1; NbExp=3; IntAct=EBI-6255752, EBI-25875545;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=1;
CC         IsoId=Q6PII5-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q6PII5-2; Sequence=VSP_030054;
CC       Name=3;
CC         IsoId=Q6PII5-3; Sequence=VSP_030053, VSP_030055;
CC       Name=4;
CC         IsoId=Q6PII5-4; Sequence=VSP_030052, VSP_030056;
CC   -!- SIMILARITY: Belongs to the metallo-beta-lactamase superfamily.
CC       Glyoxalase II family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAK61250.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC       Sequence=BAD92568.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=BAD92568.1; Type=Miscellaneous discrepancy; Note=Sequence of unknown origin at the C-terminus.; Evidence={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; AK054841; BAB70814.1; -; mRNA.
DR   EMBL; AE006464; AAK61250.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; Z98258; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471112; EAW85726.1; -; Genomic_DNA.
DR   EMBL; CH471112; EAW85730.1; -; Genomic_DNA.
DR   EMBL; CH471112; EAW85731.1; -; Genomic_DNA.
DR   EMBL; CH471112; EAW85732.1; -; Genomic_DNA.
DR   EMBL; CH471112; EAW85733.1; -; Genomic_DNA.
DR   EMBL; BC004353; AAH04353.1; -; mRNA.
DR   EMBL; BC015008; AAH15008.1; -; mRNA.
DR   EMBL; BC033796; AAH33796.1; -; mRNA.
DR   EMBL; AB209331; BAD92568.1; ALT_SEQ; mRNA.
DR   CCDS; CCDS32354.1; -. [Q6PII5-2]
DR   CCDS; CCDS32355.1; -. [Q6PII5-1]
DR   RefSeq; NP_001277066.1; NM_001290137.1. [Q6PII5-2]
DR   RefSeq; NP_001277068.1; NM_001290139.1. [Q6PII5-2]
DR   RefSeq; NP_001310564.1; NM_001323635.1. [Q6PII5-2]
DR   RefSeq; NP_115680.1; NM_032304.3. [Q6PII5-2]
DR   RefSeq; XP_005255688.1; XM_005255631.4.
DR   RefSeq; XP_011521013.1; XM_011522711.1.
DR   RefSeq; XP_016879262.1; XM_017023773.1.
DR   AlphaFoldDB; Q6PII5; -.
DR   SMR; Q6PII5; -.
DR   BioGRID; 123991; 7.
DR   IntAct; Q6PII5; 6.
DR   MINT; Q6PII5; -.
DR   STRING; 9606.ENSP00000374353; -.
DR   iPTMnet; Q6PII5; -.
DR   PhosphoSitePlus; Q6PII5; -.
DR   BioMuta; HAGHL; -.
DR   DMDM; 74737738; -.
DR   EPD; Q6PII5; -.
DR   jPOST; Q6PII5; -.
DR   MassIVE; Q6PII5; -.
DR   MaxQB; Q6PII5; -.
DR   PaxDb; 9606-ENSP00000374353; -.
DR   PeptideAtlas; Q6PII5; -.
DR   ProteomicsDB; 67158; -. [Q6PII5-1]
DR   ProteomicsDB; 67159; -. [Q6PII5-2]
DR   ProteomicsDB; 67160; -. [Q6PII5-3]
DR   ProteomicsDB; 67161; -. [Q6PII5-4]
DR   Antibodypedia; 59077; 188 antibodies from 13 providers.
DR   DNASU; 84264; -.
DR   Ensembl; ENST00000341413.8; ENSP00000341952.4; ENSG00000103253.19. [Q6PII5-1]
DR   Ensembl; ENST00000389703.8; ENSP00000374353.3; ENSG00000103253.19. [Q6PII5-2]
DR   Ensembl; ENST00000549114.5; ENSP00000447170.1; ENSG00000103253.19. [Q6PII5-3]
DR   Ensembl; ENST00000564537.5; ENSP00000457219.1; ENSG00000103253.19. [Q6PII5-3]
DR   GeneID; 84264; -.
DR   KEGG; hsa:84264; -.
DR   MANE-Select; ENST00000389703.8; ENSP00000374353.3; NM_032304.4; NP_115680.1. [Q6PII5-2]
DR   UCSC; uc002cjl.1; human. [Q6PII5-1]
DR   AGR; HGNC:14177; -.
DR   CTD; 84264; -.
DR   DisGeNET; 84264; -.
DR   GeneCards; HAGHL; -.
DR   HGNC; HGNC:14177; HAGHL.
DR   HPA; ENSG00000103253; Tissue enhanced (brain).
DR   neXtProt; NX_Q6PII5; -.
DR   OpenTargets; ENSG00000103253; -.
DR   PharmGKB; PA29180; -.
DR   VEuPathDB; HostDB:ENSG00000103253; -.
DR   eggNOG; KOG0813; Eukaryota.
DR   GeneTree; ENSGT00940000161924; -.
DR   HOGENOM; CLU_030571_4_4_1; -.
DR   InParanoid; Q6PII5; -.
DR   OMA; CKERARF; -.
DR   OrthoDB; 5471651at2759; -.
DR   PhylomeDB; Q6PII5; -.
DR   TreeFam; TF105273; -.
DR   PathwayCommons; Q6PII5; -.
DR   SignaLink; Q6PII5; -.
DR   BioGRID-ORCS; 84264; 12 hits in 1160 CRISPR screens.
DR   ChiTaRS; HAGHL; human.
DR   GenomeRNAi; 84264; -.
DR   Pharos; Q6PII5; Tbio.
DR   PRO; PR:Q6PII5; -.
DR   Proteomes; UP000005640; Chromosome 16.
DR   RNAct; Q6PII5; Protein.
DR   Bgee; ENSG00000103253; Expressed in pancreatic ductal cell and 157 other cell types or tissues.
DR   ExpressionAtlas; Q6PII5; baseline and differential.
DR   GO; GO:0004416; F:hydroxyacylglutathione hydrolase activity; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   CDD; cd07723; hydroxyacylglutathione_hydrolase_MBL-fold; 1.
DR   Gene3D; 3.60.15.10; Ribonuclease Z/Hydroxyacylglutathione hydrolase-like; 1.
DR   InterPro; IPR035680; Clx_II_MBL.
DR   InterPro; IPR001279; Metallo-B-lactamas.
DR   InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR   PANTHER; PTHR11935; BETA LACTAMASE DOMAIN; 1.
DR   PANTHER; PTHR11935:SF77; HYDROXYACYLGLUTATHIONE HYDROLASE-LIKE PROTEIN; 1.
DR   Pfam; PF00753; Lactamase_B; 1.
DR   SMART; SM00849; Lactamase_B; 1.
DR   SUPFAM; SSF56281; Metallo-hydrolase/oxidoreductase; 1.
DR   Genevisible; Q6PII5; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Hydrolase; Metal-binding; Reference proteome; Zinc.
FT   CHAIN           1..290
FT                   /note="Hydroxyacylglutathione hydrolase-like protein"
FT                   /id="PRO_0000313601"
FT   BINDING         54
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         56
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         58
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         59
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         110
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         134
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         134
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         172
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         97..203
FT                   /note="FGAIHVRCLLTPGHTAGHMSYFLWEDDCPDPPALFSGDALSVAGCGSCLEGS
FT                   AQQMYQSLAELGTLPPETKVFCGHEHTLSNLEFAQKVEPCNDHVRAKLSWAKARP ->
FT                   VSARSREGRGGRPGSTRPHRSACSSAAVRGHPRALPPDARPHRRPHELLPVGGRLPGPT
FT                   RPVLGRRAVGGRLRLVPGGQRPADVPEPGRAGYPAPRDEGVLRPRAHA (in
FT                   isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_030052"
FT   VAR_SEQ         134..202
FT                   /note="DALSVAGCGSCLEGSAQQMYQSLAELGTLPPETKVFCGHEHTLSNLEFAQKV
FT                   EPCNDHVRAKLSWAKAR -> TRSAERAHPASRRPRPICSDPPSPARRRAVGGRLRLVP
FT                   GGQRPADVPEPGRAGYPAPRDEGVLRPRAHA (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_030053"
FT   VAR_SEQ         201..290
FT                   /note="ARPLSRRGKRVGGEGTGFGVGGALRQGLMVTGACGHSRRGMRMTCPLCRRLW
FT                   ARSASTTPSCGWREYGCCPGASTVTWTLRKASGDCVLG -> KRDEDDVPTVPSTLGEE
FT                   RLYNPFLRVAEEPVRKFTGKAVPADVLEALCKERARFEQAGEPRQPQARALLALQWGLL
FT                   SAAPHD (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_030054"
FT   VAR_SEQ         203..290
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_030055"
FT   VAR_SEQ         204..290
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_030056"
SQ   SEQUENCE   290 AA;  31557 MW;  C0B2D01D53262AB2 CRC64;
     MKVKVIPVLE DNYMYLVIEE LTREAVAVDV AVPKRLLEIV GREGVSLTAV LTTHHHWDHA
     RGNPELARLR PGLAVLGADE RIFSLTRRLA HGEELRFGAI HVRCLLTPGH TAGHMSYFLW
     EDDCPDPPAL FSGDALSVAG CGSCLEGSAQ QMYQSLAELG TLPPETKVFC GHEHTLSNLE
     FAQKVEPCND HVRAKLSWAK ARPLSRRGKR VGGEGTGFGV GGALRQGLMV TGACGHSRRG
     MRMTCPLCRR LWARSASTTP SCGWREYGCC PGASTVTWTL RKASGDCVLG
//