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   02-SEP-2026, entry version 197.
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 SCAR34 PRO-100, AND CHARACTERIZATION OF VARIANT SCAR34 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: Spinocerebellar ataxia, autosomal recessive, 34 (SCAR34)
CC       [MIM:613227]: A form of spinocerebellar ataxia, a clinically and
CC       genetically heterogeneous group of cerebellar disorders due to
CC       degeneration of the cerebellum with variable involvement of the
CC       brainstem and spinal cord. SCAR34 is characterized by 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_001321837.2.
DR   RefSeq; NP_001308767.1; NM_001321838.2.
DR   RefSeq; NP_001308768.1; NM_001321839.2.
DR   RefSeq; NP_004047.3; NM_004056.6.
DR   PDB; 2W2J; X-ray; 1.60 A; A=1-290.
DR   AlphaFoldDB; P35219; -.
DR   SMR; P35219; -.
DR   BioGRID; 107222; 42.
DR   FunCoup; P35219; 62.
DR   IntAct; P35219; 38.
DR   MINT; P35219; -.
DR   NDEx; IQUERY-CP-CA8; 1 NDEx IQuery Curated Pathway.
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   jPOST; P35219; -.
DR   MassIVE; P35219; -.
DR   PaxDb; 9606-ENSP00000314407; -.
DR   PeptideAtlas; P35219; -.
DR   ProteomicsDB; 54985; -.
DR   Pumba; P35219; -.
DR   Antibodypedia; 11840; 318 antibodies from 37 providers.
DR   CPTC; P35219; 2 antibodies.
DR   DNASU; 767; -.
DR   Ensembl; ENST00000317995.5; ENSP00000314407.4; ENSG00000178538.11.
DR   Ensembl; ENST00000943617.1; ENSP00000613676.1; ENSG00000178538.11.
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   AGR; HGNC:1382; -.
DR   ClinPGx; PA25997; -.
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   OpenTargets; ENSG00000178538; -.
DR   Orphanet; 1766; Dysequilibrium syndrome.
DR   VEuPathDB; HostDB:ENSG00000178538; -.
DR   eggNOG; KOG0382; Eukaryota.
DR   GeneTree; ENSGT00940000158863; -.
DR   HOGENOM; CLU_039326_2_1_1; -.
DR   InParanoid; P35219; -.
DR   OMA; CTEGIVW; -.
DR   OrthoDB; 429145at2759; -.
DR   PAN-GO; P35219; 0 GO annotations based on evolutionary models.
DR   PhylomeDB; P35219; -.
DR   BRENDA; 4.2.1.1; 2681.
DR   PathwayCommons; P35219; -.
DR   SignaLink; P35219; -.
DR   Agora; ENSG00000178538; -.
DR   BioGRID-ORCS; 767; 14 hits in 1158 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 118 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR   GO; GO:0004089; F:carbonate dehydratase activity; TAS:ProtInc.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   CDD; cd03120; alpha_CARP_VIII; 1.
DR   DisProt; DP04094; -.
DR   FunFam; 3.10.200.10:FF:000006; Carbonic anhydrase-related protein-like; 1.
DR   Gene3D; 3.10.200.10; Alpha carbonic anhydrase; 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; CARBONIC ANHYDRASE; 1.
DR   PANTHER; PTHR18952:SF104; CARBONIC ANHYDRASE-RELATED PROTEIN; 1.
DR   Pfam; PF00194; Carb_anhydrase; 1.
DR   SMART; SM01057; Carb_anhydrase; 1.
DR   SUPFAM; SSF51069; Carbonic anhydrase; 1.
DR   PROSITE; PS00162; ALPHA_CA_1; 1.
DR   PROSITE; PS51144; ALPHA_CA_2; 1.
DR   PDBsum; 2W2J; -.
PE   1: Evidence at protein level;
KW   3D-structure; Disease variant; Intellectual disability; Metal-binding;
KW   Phosphoprotein; Proteomics identification; 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   COMPBIAS        16..26
FT                   /note="Acidic residues"
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 SCAR34; 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           186..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   HELIX           260..263
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   HELIX           275..277
FT                   /evidence="ECO:0007829|PDB:2W2J"
FT   HELIX           283..285
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
//