SPEB_HUMAN
ID SPEB_HUMAN Reviewed; 352 AA.
AC Q9BSE5; Q5TDH1; Q9H5J3;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Agmatinase, mitochondrial;
DE EC=3.5.3.11 {ECO:0000269|PubMed:11914032};
DE AltName: Full=Agmatine ureohydrolase;
DE Short=AUH;
DE Flags: Precursor;
GN Name=AGMAT;
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], TISSUE SPECIFICITY, AND VARIANTS ARG-105 AND
RP GLN-140.
RC TISSUE=Kidney;
RX PubMed=11804860; DOI=10.1152/ajpgi.00386.2001;
RA Mistry S.K., Burwell T.J., Chambers R.M., Rudolph-Owen L., Spaltmann F.,
RA Cook W.J., Morris S.M. Jr.;
RT "Cloning of human agmatinase. An alternate path for polyamine synthesis
RT induced in liver by hepatitis B virus.";
RL Am. J. Physiol. 282:G375-G381(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-105.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-105.
RC TISSUE=Ovary;
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 [5]
RP CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=11914032; DOI=10.1006/mgme.2001.3277;
RA Iyer R.K., Kim H.K., Tsoa R.W., Grody W.W., Cederbaum S.D.;
RT "Cloning and characterization of human agmatinase.";
RL Mol. Genet. Metab. 75:209-218(2002).
RN [6]
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=agmatine + H2O = putrescine + urea; Xref=Rhea:RHEA:13929,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:16199, ChEBI:CHEBI:58145,
CC ChEBI:CHEBI:326268; EC=3.5.3.11;
CC Evidence={ECO:0000269|PubMed:11914032};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00742};
CC -!- PATHWAY: Amine and polyamine biosynthesis; putrescine biosynthesis via
CC agmatine pathway; putrescine from agmatine: step 1/1.
CC {ECO:0000305|PubMed:11914032}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion.
CC -!- TISSUE SPECIFICITY: Highly expressed in liver and kidney. Also found in
CC skeletal muscle, fetal liver, brain, testis, skin and the
CC gastrointestinal tract. Within brain, expression is higher in the
CC cerebral cortex with lower levels in the medulla and spinal cord.
CC {ECO:0000269|PubMed:11804860, ECO:0000269|PubMed:11914032}.
CC -!- SIMILARITY: Belongs to the arginase family. Agmatinase subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00742}.
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DR EMBL; AY057097; AAL24446.1; -; mRNA.
DR EMBL; AK027037; BAB15633.1; -; mRNA.
DR EMBL; AL121992; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC005090; AAH05090.1; -; mRNA.
DR CCDS; CCDS160.1; -.
DR RefSeq; NP_079034.3; NM_024758.4.
DR AlphaFoldDB; Q9BSE5; -.
DR SMR; Q9BSE5; -.
DR BioGRID; 122909; 50.
DR IntAct; Q9BSE5; 5.
DR STRING; 9606.ENSP00000364986; -.
DR iPTMnet; Q9BSE5; -.
DR PhosphoSitePlus; Q9BSE5; -.
DR BioMuta; AGMAT; -.
DR DMDM; 126302602; -.
DR EPD; Q9BSE5; -.
DR jPOST; Q9BSE5; -.
DR MassIVE; Q9BSE5; -.
DR MaxQB; Q9BSE5; -.
DR PaxDb; Q9BSE5; -.
DR PeptideAtlas; Q9BSE5; -.
DR PRIDE; Q9BSE5; -.
DR ProteomicsDB; 78882; -.
DR Antibodypedia; 14379; 93 antibodies from 20 providers.
DR DNASU; 79814; -.
DR Ensembl; ENST00000375826.4; ENSP00000364986.3; ENSG00000116771.6.
DR GeneID; 79814; -.
DR KEGG; hsa:79814; -.
DR MANE-Select; ENST00000375826.4; ENSP00000364986.3; NM_024758.5; NP_079034.3.
DR UCSC; uc001awv.3; human.
DR CTD; 79814; -.
DR DisGeNET; 79814; -.
DR GeneCards; AGMAT; -.
DR HGNC; HGNC:18407; AGMAT.
DR HPA; ENSG00000116771; Group enriched (kidney, liver, skeletal muscle).
DR MIM; 617887; gene.
DR neXtProt; NX_Q9BSE5; -.
DR OpenTargets; ENSG00000116771; -.
DR PharmGKB; PA24619; -.
DR VEuPathDB; HostDB:ENSG00000116771; -.
DR eggNOG; KOG2964; Eukaryota.
DR GeneTree; ENSGT00950000183195; -.
DR HOGENOM; CLU_039478_0_0_1; -.
DR InParanoid; Q9BSE5; -.
DR OMA; YELTTIM; -.
DR OrthoDB; 921352at2759; -.
DR PhylomeDB; Q9BSE5; -.
DR TreeFam; TF328612; -.
DR BioCyc; MetaCyc:HS04051-MON; -.
DR BRENDA; 3.5.3.11; 2681.
DR PathwayCommons; Q9BSE5; -.
DR Reactome; R-HSA-351143; Agmatine biosynthesis.
DR SignaLink; Q9BSE5; -.
DR UniPathway; UPA00534; UER00287.
DR BioGRID-ORCS; 79814; 16 hits in 1069 CRISPR screens.
DR ChiTaRS; AGMAT; human.
DR GeneWiki; Agmatinase; -.
DR GenomeRNAi; 79814; -.
DR Pharos; Q9BSE5; Tbio.
DR PRO; PR:Q9BSE5; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9BSE5; protein.
DR Bgee; ENSG00000116771; Expressed in renal glomerulus and 146 other tissues.
DR ExpressionAtlas; Q9BSE5; baseline and differential.
DR Genevisible; Q9BSE5; HS.
DR GO; GO:0005739; C:mitochondrion; TAS:Reactome.
DR GO; GO:0008783; F:agmatinase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0097055; P:agmatine biosynthetic process; TAS:Reactome.
DR GO; GO:0033389; P:putrescine biosynthetic process from arginine, using agmatinase; IBA:GO_Central.
DR GO; GO:0008295; P:spermidine biosynthetic process; IEA:UniProtKB-KW.
DR InterPro; IPR005925; Agmatinase-rel.
DR InterPro; IPR006035; Ureohydrolase.
DR InterPro; IPR023696; Ureohydrolase_dom_sf.
DR InterPro; IPR020855; Ureohydrolase_Mn_BS.
DR PANTHER; PTHR11358; PTHR11358; 1.
DR Pfam; PF00491; Arginase; 1.
DR PIRSF; PIRSF036979; Arginase; 1.
DR PRINTS; PR00116; ARGINASE.
DR SUPFAM; SSF52768; SSF52768; 1.
DR TIGRFAMs; TIGR01230; agmatinase; 1.
DR PROSITE; PS01053; ARGINASE_1; 1.
DR PROSITE; PS51409; ARGINASE_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Hydrolase; Manganese; Metal-binding; Mitochondrion;
KW Putrescine biosynthesis; Reference proteome; Spermidine biosynthesis;
KW Transit peptide.
FT TRANSIT 1..35
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 36..352
FT /note="Agmatinase, mitochondrial"
FT /id="PRO_0000002089"
FT REGION 11..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 162
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00742"
FT BINDING 185
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00742"
FT BINDING 185
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00742"
FT BINDING 187
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00742"
FT BINDING 189
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00742"
FT BINDING 276
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00742"
FT BINDING 276
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00742"
FT BINDING 278
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00742"
FT MOD_RES 193
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:A2AS89"
FT MOD_RES 217
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:A2AS89"
FT MOD_RES 217
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:A2AS89"
FT VARIANT 105
FT /note="G -> R (in dbSNP:rs6429757)"
FT /evidence="ECO:0000269|PubMed:11804860,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT /id="VAR_023485"
FT VARIANT 140
FT /note="R -> Q (in dbSNP:rs11580170)"
FT /evidence="ECO:0000269|PubMed:11804860"
FT /id="VAR_048332"
FT CONFLICT 145
FT /note="Y -> C (in Ref. 2; BAB15633)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 352 AA; 37660 MW; 394738202353314A CRC64;
MLRLLASGCA RGPGPGVGAR PAAGLFHPGR RQSRQASDAP RNQPPSPEFV ARPVGVCSMM
RLPVQTSPEG LDAAFIGVPL DTGTSNRPGA RFGPRRIREE SVMLGTVNPS TGALPFQSLM
VADLGDVNVN LYNLQDSCRR IQEAYEKIVA AGCIPLTLGG DHTITYPILQ AMAKKHGPVG
LLHVDAHTDT TDKALGEKLY HGAPFRRCVD EGLLDCKRVV QIGIRGSSTT LDPYRYNRSQ
GFRVVLAEDC WMKSLVPLMG EVRQQMGGKP IYISFDIDAL DPAYAPGTGT PEIAGLTPSQ
ALEIIRGCQG LNVMGCDLVE VSPPYDLSGN TALLAANLLF EMLCALPKVT TV
