CAH8_HUMAN
ID CAH8_HUMAN Reviewed; 290 AA.
AC P35219; A8K0A5; B3KQZ7; Q32MY2;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Carbonic anhydrase-related protein;
DE Short=CARP;
DE AltName: Full=Carbonic anhydrase VIII;
DE Short=CA-VIII;
GN Name=CA8; Synonyms=CALS;
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].
RX PubMed=8482548; DOI=10.1016/0378-1119(93)90385-g;
RA Skaggs L.A., Bergenhem N.C.H., Venta P.J., Tashian R.E.;
RT "The deduced amino acid sequence of human carbonic anhydrase-related
RT protein (CARP) is 98% identical to the mouse homologue.";
RL Gene 126:291-292(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Chen Y., Huang C.-H.;
RT "Molecular identification of carbonic anhydrases (CA) and CA-related (CAR)
RT genes.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [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].
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 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 X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
RX PubMed=19360879; DOI=10.1002/prot.22411;
RA Picaud S.S., Muniz J.R.C., Kramm A., Pilka E.S., Kochan G., Oppermann U.,
RA Yue W.W.;
RT "Crystal structure of human carbonic anhydrase-related protein VIII reveals
RT the basis for catalytic silencing.";
RL Proteins 76:507-511(2009).
RN [8]
RP VARIANT CMARQ3 PRO-100, AND CHARACTERIZATION OF VARIANT CMARQ3 PRO-100.
RX PubMed=19461874; DOI=10.1371/journal.pgen.1000487;
RA Turkmen S., Guo G., Garshasbi M., Hoffmann K., Alshalah A.J., Mischung C.,
RA Kuss A., Humphrey N., Mundlos S., Robinson P.N.;
RT "CA8 mutations cause a novel syndrome characterized by ataxia and mild
RT mental retardation with predisposition to quadrupedal gait.";
RL PLoS Genet. 5:E1000487-E1000487(2009).
CC -!- FUNCTION: Does not have a carbonic anhydrase catalytic activity.
CC -!- INTERACTION:
CC P35219; O43186: CRX; NbExp=7; IntAct=EBI-718700, EBI-748171;
CC P35219; Q9UJY4: GGA2; NbExp=6; IntAct=EBI-718700, EBI-447646;
CC P35219; Q9BPX1: HSD17B14; NbExp=14; IntAct=EBI-718700, EBI-742664;
CC P35219; Q9NVH2: INTS7; NbExp=3; IntAct=EBI-718700, EBI-11276282;
CC P35219; Q9P2G9-2: KLHL8; NbExp=3; IntAct=EBI-718700, EBI-11959635;
CC P35219; Q03252: LMNB2; NbExp=3; IntAct=EBI-718700, EBI-2830427;
CC P35219; Q8TBB1: LNX1; NbExp=6; IntAct=EBI-718700, EBI-739832;
CC P35219; Q9Y5V3: MAGED1; NbExp=9; IntAct=EBI-718700, EBI-716006;
CC P35219; Q9BZG1: RAB34; NbExp=3; IntAct=EBI-718700, EBI-2856739;
CC P35219; Q96EA4: SPDL1; NbExp=6; IntAct=EBI-718700, EBI-715381;
CC P35219; O15119: TBX3; NbExp=3; IntAct=EBI-718700, EBI-3452216;
CC -!- DISEASE: Cerebellar ataxia, intellectual disability, and dysequilibrium
CC syndrome 3 (CMARQ3) [MIM:613227]: An autosomal recessive, congenital
CC cerebellar ataxia associated with dysarthia, quadrupedal gait and
CC intellectual disability. {ECO:0000269|PubMed:19461874}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the alpha-carbonic anhydrase family.
CC {ECO:0000305}.
CC -!- CAUTION: Although it belongs to the alpha-carbonic anhydrase family,
CC Arg-116 is present instead of the conserved His which is a zinc-binding
CC residue. It is therefore expected that this protein lacks carbonic
CC anhydrase activity. {ECO:0000305}.
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DR EMBL; L04656; AAA35653.2; -; mRNA.
DR EMBL; AY075022; AAL78170.1; -; mRNA.
DR EMBL; AK289470; BAF82159.1; -; mRNA.
DR EMBL; AK314538; BAG37128.1; -; mRNA.
DR EMBL; AK090655; BAG52209.1; -; mRNA.
DR EMBL; CH471068; EAW86826.1; -; Genomic_DNA.
DR EMBL; BC069744; AAH69744.1; -; mRNA.
DR EMBL; BC069794; AAH69794.1; -; mRNA.
DR EMBL; BC108929; AAI08930.1; -; mRNA.
DR CCDS; CCDS6174.1; -.
DR PIR; JN0576; JN0576.
DR RefSeq; NP_001308766.1; NM_001321837.1.
DR RefSeq; NP_001308767.1; NM_001321838.1.
DR RefSeq; NP_001308768.1; NM_001321839.1.
DR RefSeq; NP_004047.3; NM_004056.5.
DR PDB; 2W2J; X-ray; 1.60 A; A=1-290.
DR PDBsum; 2W2J; -.
DR AlphaFoldDB; P35219; -.
DR SMR; P35219; -.
DR BioGRID; 107222; 38.
DR IntAct; P35219; 35.
DR MINT; P35219; -.
DR STRING; 9606.ENSP00000314407; -.
DR DrugBank; DB00909; Zonisamide.
DR GlyGen; P35219; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P35219; -.
DR PhosphoSitePlus; P35219; -.
DR BioMuta; CA8; -.
DR DMDM; 461681; -.
DR EPD; P35219; -.
DR jPOST; P35219; -.
DR MassIVE; P35219; -.
DR MaxQB; P35219; -.
DR PaxDb; P35219; -.
DR PeptideAtlas; P35219; -.
DR PRIDE; P35219; -.
DR ProteomicsDB; 54985; -.
DR Antibodypedia; 11840; 292 antibodies from 35 providers.
DR CPTC; P35219; 2 antibodies.
DR DNASU; 767; -.
DR Ensembl; ENST00000317995.5; ENSP00000314407.4; ENSG00000178538.10.
DR GeneID; 767; -.
DR KEGG; hsa:767; -.
DR MANE-Select; ENST00000317995.5; ENSP00000314407.4; NM_004056.6; NP_004047.3.
DR UCSC; uc003xtz.2; human.
DR CTD; 767; -.
DR DisGeNET; 767; -.
DR GeneCards; CA8; -.
DR HGNC; HGNC:1382; CA8.
DR HPA; ENSG00000178538; Tissue enhanced (brain, parathyroid gland).
DR MalaCards; CA8; -.
DR MIM; 114815; gene.
DR MIM; 613227; phenotype.
DR neXtProt; NX_P35219; -.
DR OpenTargets; ENSG00000178538; -.
DR Orphanet; 1766; Dysequilibrium syndrome.
DR PharmGKB; PA25997; -.
DR VEuPathDB; HostDB:ENSG00000178538; -.
DR eggNOG; KOG0382; Eukaryota.
DR GeneTree; ENSGT00940000158863; -.
DR HOGENOM; CLU_039326_2_1_1; -.
DR InParanoid; P35219; -.
DR OMA; THNEREM; -.
DR OrthoDB; 1377476at2759; -.
DR PhylomeDB; P35219; -.
DR TreeFam; TF316425; -.
DR BRENDA; 4.2.1.1; 2681.
DR PathwayCommons; P35219; -.
DR SignaLink; P35219; -.
DR BioGRID-ORCS; 767; 13 hits in 1078 CRISPR screens.
DR ChiTaRS; CA8; human.
DR EvolutionaryTrace; P35219; -.
DR GeneWiki; CA8; -.
DR GenomeRNAi; 767; -.
DR Pharos; P35219; Tbio.
DR PRO; PR:P35219; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P35219; protein.
DR Bgee; ENSG00000178538; Expressed in metanephros cortex and 116 other tissues.
DR Genevisible; P35219; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0004089; F:carbonate dehydratase activity; TAS:ProtInc.
DR GO; GO:0016836; F:hydro-lyase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006730; P:one-carbon metabolic process; IBA:GO_Central.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IEA:Ensembl.
DR CDD; cd03120; alpha_CARP_VIII; 1.
DR Gene3D; 3.10.200.10; -; 1.
DR InterPro; IPR001148; CA_dom.
DR InterPro; IPR036398; CA_dom_sf.
DR InterPro; IPR023561; Carbonic_anhydrase_a-class.
DR InterPro; IPR018338; Carbonic_anhydrase_a-class_CS.
DR InterPro; IPR041877; CARP_VIII.
DR PANTHER; PTHR18952; PTHR18952; 1.
DR Pfam; PF00194; Carb_anhydrase; 1.
DR SMART; SM01057; Carb_anhydrase; 1.
DR SUPFAM; SSF51069; SSF51069; 1.
DR PROSITE; PS00162; ALPHA_CA_1; 1.
DR PROSITE; PS51144; ALPHA_CA_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disease variant; Intellectual disability; Metal-binding;
KW Phosphoprotein; Reference proteome; Zinc.
FT CHAIN 1..290
FT /note="Carbonic anhydrase-related protein"
FT /id="PRO_0000077433"
FT DOMAIN 27..289
FT /note="Alpha-carbonic anhydrase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01134"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 87
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P00918"
FT BINDING 118
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255"
FT BINDING 141
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255"
FT SITE 116
FT /note="Ancestral zinc ligand"
FT MOD_RES 5
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5PPN4"
FT VARIANT 100
FT /note="S -> P (in CMARQ3; affects protein stability owing
FT to accelerated proteasomal degradation; dbSNP:rs267606695)"
FT /evidence="ECO:0000269|PubMed:19461874"
FT /id="VAR_063634"
FT CONFLICT 106
FT /note="Q -> R (in Ref. 3; BAG52209)"
FT /evidence="ECO:0000305"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:2W2J"
FT HELIX 37..39
FT /evidence="ECO:0007829|PDB:2W2J"
FT HELIX 42..45
FT /evidence="ECO:0007829|PDB:2W2J"
FT HELIX 56..58
FT /evidence="ECO:0007829|PDB:2W2J"
FT HELIX 63..66
FT /evidence="ECO:0007829|PDB:2W2J"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:2W2J"
FT STRAND 77..84
FT /evidence="ECO:0007829|PDB:2W2J"
FT STRAND 89..92
FT /evidence="ECO:0007829|PDB:2W2J"
FT STRAND 97..101
FT /evidence="ECO:0007829|PDB:2W2J"
FT STRAND 110..119
FT /evidence="ECO:0007829|PDB:2W2J"
FT STRAND 128..131
FT /evidence="ECO:0007829|PDB:2W2J"
FT STRAND 137..146
FT /evidence="ECO:0007829|PDB:2W2J"
FT TURN 147..149
FT /evidence="ECO:0007829|PDB:2W2J"
FT HELIX 153..156
FT /evidence="ECO:0007829|PDB:2W2J"
FT STRAND 163..174
FT /evidence="ECO:0007829|PDB:2W2J"
FT HELIX 177..183
FT /evidence="ECO:0007829|PDB:2W2J"
FT HELIX 184..189
FT /evidence="ECO:0007829|PDB:2W2J"
FT STRAND 194..199
FT /evidence="ECO:0007829|PDB:2W2J"
FT HELIX 203..206
FT /evidence="ECO:0007829|PDB:2W2J"
FT STRAND 215..221
FT /evidence="ECO:0007829|PDB:2W2J"
FT STRAND 229..238
FT /evidence="ECO:0007829|PDB:2W2J"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:2W2J"
FT HELIX 244..250
FT /evidence="ECO:0007829|PDB:2W2J"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:2W2J"
FT STRAND 286..288
FT /evidence="ECO:0007829|PDB:2W2J"
SQ SEQUENCE 290 AA; 32973 MW; C142711660A972DB CRC64;
MADLSFIEDT VAFPEKEEDE EEEEEGVEWG YEEGVEWGLV FPDANGEYQS PINLNSREAR
YDPSLLDVRL SPNYVVCRDC EVTNDGHTIQ VILKSKSVLS GGPLPQGHEF ELYEVRFHWG
RENQRGSEHT VNFKAFPMEL HLIHWNSTLF GSIDEAVGKP HGIAIIALFV QIGKEHVGLK
AVTEILQDIQ YKGKSKTIPC FNPNTLLPDP LLRDYWVYEG SLTIPPCSEG VTWILFRYPL
TISQLQIEEF RRLRTHVKGA ELVEGCDGIL GDNFRPTQPL SDRVIRAAFQ
