FHDC1_HUMAN
ID FHDC1_HUMAN Reviewed; 1143 AA.
AC Q9C0D6;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=FH2 domain-containing protein 1;
DE AltName: Full=Inverted formin-1 {ECO:0000303|PubMed:18815276};
GN Name=FHDC1; Synonyms=INF1 {ECO:0000303|PubMed:18815276}, KIAA1727;
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 GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 14-1143, AND VARIANT CYS-639.
RC TISSUE=Brain;
RX PubMed=11214970; DOI=10.1093/dnares/7.6.347;
RA Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:347-355(2000).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND REGION MTBD.
RX PubMed=18815276; DOI=10.1091/mbc.e08-05-0469;
RA Young K.G., Thurston S.F., Copeland S., Smallwood C., Copeland J.W.;
RT "INF1 is a novel microtubule-associated formin.";
RL Mol. Biol. Cell 19:5168-5180(2008).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-500; SER-660 AND SER-664, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [5]
RP FUNCTION, MUTAGENESIS OF ILE-180, AND DOMAINS FH2 AND MTBD.
RX PubMed=26564798; DOI=10.1091/mbc.e15-02-0070;
RA Copeland S.J., Thurston S.F., Copeland J.W.;
RT "Actin- and microtubule-dependent regulation of Golgi morphology by
RT FHDC1.";
RL Mol. Biol. Cell 27:260-276(2016).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ILE-180.
RX PubMed=29742020; DOI=10.1091/mbc.e18-02-0088;
RA Copeland S.J., McRae A., Guarguaglini G., Trinkle-Mulcahy L.,
RA Copeland J.W.;
RT "Actin-dependent regulation of cilia length by the inverted formin FHDC1.";
RL Mol. Biol. Cell 29:1611-1627(2018).
RN [7]
RP VARIANT PHE-297.
RX PubMed=23033978; DOI=10.1056/nejmoa1206524;
RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C.,
RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G.,
RA Veltman J.A., Vissers L.E.;
RT "Diagnostic exome sequencing in persons with severe intellectual
RT disability.";
RL N. Engl. J. Med. 367:1921-1929(2012).
CC -!- FUNCTION: Microtubule-associated formin which regulates both actin and
CC microtubule dynamics. Induces microtubule acetylation and stabilization
CC and actin stress fiber formation (PubMed:18815276). Regulates Golgi
CC ribbon formation (PubMed:26564798). Required for normal cilia assembly.
CC Early in cilia assembly, may assist in the maturation and positioning
CC of the centrosome/basal body, and once cilia assembly has initiated,
CC may also promote cilia elongation by inhibiting disassembly
CC (PubMed:29742020). {ECO:0000269|PubMed:18815276,
CC ECO:0000269|PubMed:26564798, ECO:0000269|PubMed:29742020}.
CC -!- SUBUNIT: Interacts with CEP170. {ECO:0000250|UniProtKB:Q3ULZ2}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium
CC {ECO:0000269|PubMed:29742020}. Golgi apparatus
CC {ECO:0000250|UniProtKB:Q3ULZ2}. Note=Associates with microtubules.
CC {ECO:0000269|PubMed:18815276}.
CC -!- DOMAIN: The FH2 and MBD domains are essential for its function in
CC regulating Golgi ribbon formation. {ECO:0000269|PubMed:26564798}.
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DR EMBL; AC093599; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB051514; BAB21818.1; -; mRNA.
DR CCDS; CCDS34081.1; -.
DR RefSeq; NP_203751.2; NM_033393.2.
DR RefSeq; XP_005263376.1; XM_005263319.3.
DR RefSeq; XP_006714456.1; XM_006714393.3.
DR RefSeq; XP_011530690.1; XM_011532388.1.
DR RefSeq; XP_011530691.1; XM_011532389.1.
DR AlphaFoldDB; Q9C0D6; -.
DR SMR; Q9C0D6; -.
DR BioGRID; 124546; 3.
DR IntAct; Q9C0D6; 2.
DR STRING; 9606.ENSP00000427567; -.
DR iPTMnet; Q9C0D6; -.
DR PhosphoSitePlus; Q9C0D6; -.
DR BioMuta; FHDC1; -.
DR DMDM; 166977313; -.
DR EPD; Q9C0D6; -.
DR jPOST; Q9C0D6; -.
DR MassIVE; Q9C0D6; -.
DR PaxDb; Q9C0D6; -.
DR PeptideAtlas; Q9C0D6; -.
DR PRIDE; Q9C0D6; -.
DR ProteomicsDB; 80016; -.
DR Antibodypedia; 16653; 13 antibodies from 8 providers.
DR DNASU; 85462; -.
DR Ensembl; ENST00000511601.6; ENSP00000427567.1; ENSG00000137460.10.
DR GeneID; 85462; -.
DR KEGG; hsa:85462; -.
DR MANE-Select; ENST00000511601.6; ENSP00000427567.1; NM_001371116.1; NP_001358045.1.
DR UCSC; uc003inf.2; human.
DR CTD; 85462; -.
DR DisGeNET; 85462; -.
DR GeneCards; FHDC1; -.
DR HGNC; HGNC:29363; FHDC1.
DR HPA; ENSG00000137460; Tissue enhanced (bone marrow, parathyroid gland, thyroid gland).
DR neXtProt; NX_Q9C0D6; -.
DR OpenTargets; ENSG00000137460; -.
DR PharmGKB; PA162388490; -.
DR VEuPathDB; HostDB:ENSG00000137460; -.
DR eggNOG; KOG1922; Eukaryota.
DR GeneTree; ENSGT00940000155128; -.
DR HOGENOM; CLU_009023_0_0_1; -.
DR InParanoid; Q9C0D6; -.
DR OMA; LECWKQE; -.
DR OrthoDB; 1204639at2759; -.
DR PhylomeDB; Q9C0D6; -.
DR TreeFam; TF324020; -.
DR PathwayCommons; Q9C0D6; -.
DR SignaLink; Q9C0D6; -.
DR BioGRID-ORCS; 85462; 8 hits in 1077 CRISPR screens.
DR ChiTaRS; FHDC1; human.
DR GenomeRNAi; 85462; -.
DR Pharos; Q9C0D6; Tbio.
DR PRO; PR:Q9C0D6; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9C0D6; protein.
DR Bgee; ENSG00000137460; Expressed in ileal mucosa and 150 other tissues.
DR Genevisible; Q9C0D6; HS.
DR GO; GO:0005884; C:actin filament; IBA:GO_Central.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005881; C:cytoplasmic microtubule; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; ISS:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0030041; P:actin filament polymerization; IBA:GO_Central.
DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:0090161; P:Golgi ribbon formation; IMP:UniProtKB.
DR GO; GO:0043149; P:stress fiber assembly; IDA:UniProtKB.
DR Gene3D; 1.20.58.2220; -; 1.
DR InterPro; IPR015425; FH2_Formin.
DR InterPro; IPR042201; FH2_Formin_sf.
DR Pfam; PF02181; FH2; 1.
DR SMART; SM00498; FH2; 1.
DR PROSITE; PS51444; FH2; 1.
PE 1: Evidence at protein level;
KW Actin-binding; Cell projection; Cilium biogenesis/degradation;
KW Golgi apparatus; Microtubule; Phosphoprotein; Reference proteome.
FT CHAIN 1..1143
FT /note="FH2 domain-containing protein 1"
FT /id="PRO_0000317280"
FT DOMAIN 87..482
FT /note="FH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00774"
FT REGION 16..89
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 517..638
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 706..1143
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 960..1086
FT /note="MTBD; microtubule-binding domain"
FT /evidence="ECO:0000269|PubMed:18815276"
FT COMPBIAS 27..82
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 598..625
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 713..729
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 812..827
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 845..864
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 886..906
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 923..971
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 992..1015
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1069..1083
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 500
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 650
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3ULZ2"
FT MOD_RES 660
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 664
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT VARIANT 297
FT /note="L -> F"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069394"
FT VARIANT 639
FT /note="R -> C (in dbSNP:rs3811833)"
FT /evidence="ECO:0000269|PubMed:11214970"
FT /id="VAR_050990"
FT MUTAGEN 180
FT /note="I->A: Loss of actin-binding and ability to induce
FT Golgi ribbon formation. Induces a significant increase in
FT average cilia length."
FT /evidence="ECO:0000269|PubMed:26564798,
FT ECO:0000269|PubMed:29742020"
SQ SEQUENCE 1143 AA; 124762 MW; A656741E826F59CC CRC64;
MHVMNCVSLV SDKENGNIAT APGFMIGQTP PPAPPPPPPP PPPSPPCSCS REECPSSPPP
PPPPPLPGEP PIPPPPPGLP PTTHMNGYSH LGKKKRMRSF FWKTIPEEQV RGKTNIWTLA
ARQEHHYQID TKTIEELFGQ QEDTTKSSLP RRGRTLNSSF REAREEITIL DAKRSMNIGI
FLKQFKKSPR SIVEDIHQGK SEHYGSETLR EFLKFLPESE EVKKLKAFSG DVSKLSLADS
FLYGLIQVPN YSLRIEAMVL KKEFLPSCSS LYTDITVLRT AIKELMSCEE LHSILHLVLQ
AGNIMNAGGY AGNAVGFKLS SLLKLADTKA NKPGMNLLHF VAQEAQKKDT ILLNFSEKLH
HVQKTARLSL ENTEAELHLL FVRTKSLKEN IQRDGELCQQ MEDFLQFAIE KLRELECWKQ
ELQDEAYTLI DFFCEDKKTM KLDECFQIFR DFCTKFNKAV KDNHDREAQE LRQLQRLKEQ
EQKQRSWATG ELGAFGRSSS ENDVELLTKK GAEGLLPFLH PRPISPSSPS YRPPNTRRSR
LSLGPSADRE LLTFLESSTG SPEEPNKFHS LPRSSPRQAR PTIACLEPAE VRHQDSSFAH
KPQASGGQEE APNPPSAQAH QLAAAQPENH ASAFPRARRQ GVSVLRKRYS EPVSLGSAQS
PPLSPLALGI KEHELVTGLA QFNLQGSQGM EETSQLTLSD FSPMELESVG HRGPQSLSAS
SSSLTPMGRD ALGSLSPALE DGKAAPDEPG SAALGSVGSS DPENKDPRPL FCISDTTDCS
LTLDCSEGTD SRPRGGDPEE GGEGDGSMSS GVGEMGDSQV SSNPTSSPPG EAPAPVSVDS
EPSCKGGLPR DKPTKRKDVV APKRGSLKEA SPGASKPGSA RRSQGAVAKS VRTLTASENE
SMRKVMPITK SSRGAGWRRP ELSSRGPSQN PPSSTDTVWS RQNSVRRAST GAEEQRLPRG
SSGSSSTRPG RDVPLQPRGS FKKPSAKPLR NLPRQKPEEN KTCRAHSEGP ESPKEEPKTP
SVPSVPHELP RVPSFARNTV ASSSRSMRTD LPPVAKAPGI TRTVSQRQLR VKGDPEDAAP
KDSSTLRRAS SARAPKKRPE SAEGPSANTE APLKARGAGE RASLRRKDSS RTTLGRILNP
LRK
