PKHH2_HUMAN
ID PKHH2_HUMAN Reviewed; 1493 AA.
AC Q8IVE3; Q5JPJ6; Q6P4Q1; Q8N3Q3;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 02-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Pleckstrin homology domain-containing family H member 2;
GN Name=PLEKHH2; Synonyms=KIAA2028;
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] (ISOFORMS 1 AND 2).
RC TISSUE=Adipose tissue, and Cervix;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Placenta;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 45-1493 (ISOFORM 1).
RC TISSUE=Brain;
RA Nagase T., Kikuno R., Ohara O.;
RT "The nucleotide sequence of a long cDNA clone isolated from human.";
RL Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=22832517; DOI=10.1038/ki.2012.252;
RA Perisic L., Lal M., Hulkko J., Hultenby K., Onfelt B., Sun Y., Duner F.,
RA Patrakka J., Betsholtz C., Uhlen M., Brismar H., Tryggvason K.,
RA Wernerson A., Pikkarainen T.;
RT "Plekhh2, a novel podocyte protein downregulated in human focal segmental
RT glomerulosclerosis, is involved in matrix adhesion and actin dynamics.";
RL Kidney Int. 82:1071-1083(2012).
CC -!- FUNCTION: In the kidney glomerulus may play a role in linking podocyte
CC foot processes to the glomerular basement membrane. May be involved in
CC stabilization of F-actin by attenuating its depolymerization. Can
CC recruit TGFB1I1 from focal adhesions to podocyte lamellipodia.
CC -!- SUBUNIT: Self-associates. Interacts with TGFB1I1 (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q8IVE3; O60711: LPXN; NbExp=4; IntAct=EBI-2815745, EBI-744222;
CC Q8IVE3-3; P49023-2: PXN; NbExp=3; IntAct=EBI-11954248, EBI-11954250;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22832517}.
CC Cytoplasm, cytoskeleton {ECO:0000269|PubMed:22832517}. Cell membrane
CC {ECO:0000269|PubMed:22832517}; Peripheral membrane protein
CC {ECO:0000269|PubMed:22832517}; Cytoplasmic side
CC {ECO:0000269|PubMed:22832517}. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:22832517}. Note=Localizes to foot process of
CC podocytes. Localization to peripheral regions of lamellipodia seems to
CC be dependent on PI3K.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8IVE3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IVE3-2; Sequence=VSP_028573;
CC Name=3;
CC IsoId=Q8IVE3-3; Sequence=VSP_028574, VSP_028575;
CC -!- TISSUE SPECIFICITY: Kidney. Reduced expression in patients with focal
CC segmental glomerulosclerosis. {ECO:0000269|PubMed:22832517}.
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DR EMBL; AL832207; CAI46132.1; -; mRNA.
DR EMBL; AL833400; CAD38637.1; -; mRNA.
DR EMBL; BC063310; AAH63310.1; -; mRNA.
DR EMBL; AB095948; BAC23124.1; -; mRNA.
DR CCDS; CCDS1812.1; -. [Q8IVE3-1]
DR RefSeq; NP_742066.2; NM_172069.3. [Q8IVE3-1]
DR RefSeq; XP_016858842.1; XM_017003353.1. [Q8IVE3-2]
DR AlphaFoldDB; Q8IVE3; -.
DR SMR; Q8IVE3; -.
DR BioGRID; 126228; 10.
DR IntAct; Q8IVE3; 7.
DR STRING; 9606.ENSP00000282406; -.
DR iPTMnet; Q8IVE3; -.
DR PhosphoSitePlus; Q8IVE3; -.
DR BioMuta; PLEKHH2; -.
DR DMDM; 158706383; -.
DR EPD; Q8IVE3; -.
DR jPOST; Q8IVE3; -.
DR MassIVE; Q8IVE3; -.
DR PaxDb; Q8IVE3; -.
DR PeptideAtlas; Q8IVE3; -.
DR PRIDE; Q8IVE3; -.
DR ProteomicsDB; 70683; -. [Q8IVE3-1]
DR ProteomicsDB; 70684; -. [Q8IVE3-2]
DR ProteomicsDB; 70685; -. [Q8IVE3-3]
DR Antibodypedia; 29827; 83 antibodies from 19 providers.
DR DNASU; 130271; -.
DR Ensembl; ENST00000282406.9; ENSP00000282406.4; ENSG00000152527.14. [Q8IVE3-1]
DR GeneID; 130271; -.
DR KEGG; hsa:130271; -.
DR MANE-Select; ENST00000282406.9; ENSP00000282406.4; NM_172069.4; NP_742066.2.
DR UCSC; uc010yny.3; human. [Q8IVE3-1]
DR CTD; 130271; -.
DR DisGeNET; 130271; -.
DR GeneCards; PLEKHH2; -.
DR HGNC; HGNC:30506; PLEKHH2.
DR HPA; ENSG00000152527; Low tissue specificity.
DR MIM; 612723; gene.
DR neXtProt; NX_Q8IVE3; -.
DR OpenTargets; ENSG00000152527; -.
DR PharmGKB; PA134912826; -.
DR VEuPathDB; HostDB:ENSG00000152527; -.
DR eggNOG; KOG0248; Eukaryota.
DR GeneTree; ENSGT00940000157675; -.
DR HOGENOM; CLU_001626_3_1_1; -.
DR InParanoid; Q8IVE3; -.
DR OMA; QTPCGSE; -.
DR OrthoDB; 75793at2759; -.
DR PhylomeDB; Q8IVE3; -.
DR TreeFam; TF312866; -.
DR PathwayCommons; Q8IVE3; -.
DR SignaLink; Q8IVE3; -.
DR BioGRID-ORCS; 130271; 11 hits in 1063 CRISPR screens.
DR ChiTaRS; PLEKHH2; human.
DR GenomeRNAi; 130271; -.
DR Pharos; Q8IVE3; Tdark.
DR PRO; PR:Q8IVE3; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q8IVE3; protein.
DR Bgee; ENSG00000152527; Expressed in calcaneal tendon and 163 other tissues.
DR ExpressionAtlas; Q8IVE3; baseline and differential.
DR Genevisible; Q8IVE3; HS.
DR GO; GO:0030864; C:cortical actin cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; ISS:UniProtKB.
DR GO; GO:0030835; P:negative regulation of actin filament depolymerization; ISS:UniProtKB.
DR CDD; cd14473; FERM_B-lobe; 1.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 1.25.40.530; -; 1.
DR Gene3D; 2.30.29.30; -; 3.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_sf.
DR InterPro; IPR035963; FERM_2.
DR InterPro; IPR019748; FERM_central.
DR InterPro; IPR000299; FERM_domain.
DR InterPro; IPR000857; MyTH4_dom.
DR InterPro; IPR038185; MyTH4_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR Pfam; PF00373; FERM_M; 1.
DR Pfam; PF00784; MyTH4; 1.
DR Pfam; PF00169; PH; 1.
DR SMART; SM00295; B41; 1.
DR SMART; SM00139; MyTH4; 1.
DR SMART; SM00233; PH; 2.
DR SUPFAM; SSF47031; SSF47031; 1.
DR PROSITE; PS50057; FERM_3; 1.
DR PROSITE; PS51016; MYTH4; 1.
DR PROSITE; PS50003; PH_DOMAIN; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Coiled coil;
KW Cytoplasm; Cytoskeleton; Membrane; Reference proteome; Repeat.
FT CHAIN 1..1493
FT /note="Pleckstrin homology domain-containing family H
FT member 2"
FT /id="PRO_0000307121"
FT DOMAIN 703..797
FT /note="PH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 811..919
FT /note="PH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 955..1110
FT /note="MyTH4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00359"
FT DOMAIN 1121..1451
FT /note="FERM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084"
FT REGION 202..230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 245..335
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 363..439
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 613..705
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1474..1493
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 20..175
FT /evidence="ECO:0000255"
FT COMPBIAS 212..230
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 245..285
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 299..335
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 373..391
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 392..409
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 624..638
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 676..702
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..563
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_028573"
FT VAR_SEQ 768..796
FT /note="LTTEKHTYYLTADSPNILEEWIKVLQNVL -> VLNFFFFFFFFVSCQTQFS
FT IIQPNGKEIG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_028574"
FT VAR_SEQ 797..1493
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_028575"
FT VARIANT 228
FT /note="M -> V (in dbSNP:rs10175843)"
FT /id="VAR_055542"
FT VARIANT 481
FT /note="P -> T (in dbSNP:rs17031297)"
FT /id="VAR_035344"
FT VARIANT 1069
FT /note="R -> K (in dbSNP:rs2278358)"
FT /id="VAR_035345"
FT VARIANT 1217
FT /note="N -> S (in dbSNP:rs17031368)"
FT /id="VAR_035346"
FT CONFLICT 451
FT /note="V -> A (in Ref. 1; CAI46132)"
FT /evidence="ECO:0000305"
FT CONFLICT 730
FT /note="G -> C (in Ref. 1; CAI46132)"
FT /evidence="ECO:0000305"
FT CONFLICT 858
FT /note="A -> V (in Ref. 1; CAI46132)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1493 AA; 168229 MW; 5B7765F5FDDE7ED0 CRC64;
MAELSEPEGP VDWKERCVAL ESQLMKFRVQ ASKIRELLAE KMQQLERQVI DAERQAEKAF
QQVQVMEDKL KAANIQTSES ETRLYNKCQD LESLIQEKDD VIQNLELQLE EQKQIRIQEA
KIIEEKAAKI KEWVTVKLNE LELENQNLRL INQNQTEEIR TMQSKLQEVQ GKKSSTVSTL
KLSEGQRLSS LTFGCFLSRA RSPPQVVKSE EMSKISSKEP EFTEGKDMEE MEIPEKSVDN
QVLENNRGQR TLHQTPCGSE QNRKTRTSFA TDGGISQNSG APVSDWSSDE EDGSKGRSKS
RCTSTLSSHT SEEGVQCSRM GSEMYLTASD DSSSIFEEET FGIKRPEHKK LYSWQQEAQW
KALNSPLGKG NSELSKKEQD SSSDELNKKF QSQRLDYSSS SSEANTPSPI LTPALMPKHP
NSLSGKGTQL VPSSHLPPPK LRIPNVFSIS VALAKRHLSQ PQLSSDRMFG TNRNAISMIR
PLRPQETDLD LVDGDSTEVL ENMDTSCDDG LFSYDSLDSP NSDDQEHCDS AKKVAYSKPP
TPPLHRFPSW ESRIYAVAKS GIRMSEAFNM ESVNKNSAAT LSYTTSGLYT SLIYKNMTTP
VYTTLKGKAT QISSSPFLDD SSGSEEEDSS RSSSRTSESD SRSRSGPGSP RAMKRGVSLS
SVASESDYAI PPDAYSTDTE YSQPEQKLPK TCSSSSDNGK NEPLEKSGYL LKMSGKVKSW
KRRWFVLKGG ELLYYKSPSD VIRKPQGHIE LSASCSILRG DNKQTVQLTT EKHTYYLTAD
SPNILEEWIK VLQNVLRVQA ANPLSLQPEG KPTMKGLLTK VKHGYSKRVW CTLIGKTLYY
FRSQEDKFPL GQIKLWEAKV EEVDRSCDSD EDYEASGRSL LSTHYTIVIH PKDQGPTYLL
IGSKHEKDTW LYHLTVAAGS NNVNVGSEFE QLVCKLLNID GEPSSQIWRH PTLCHSKEGI
ISPLTTLPSE ALQTEAIKLF KTCQLFINAA VDSPAIDYHI SLAQSALQIC LTHPELQNEI
CCQLIKQTRR RQPQNQPGPL QGWQLLALCV GLFLPHHPFL WLLRLHLKRN ADSRTEFGKY
AIYCQRCVER TQQNGDREAR PSRMEILSTL LRNPYHHSLP FSIPVHFMNG IYQVVGFDAS
TTVEEFLNTL NQDTGMRKPA QSGFALFTDD PSGRDLEHCL QGNIKICDII SKWEQASKEQ
QPGKCEGTRT VRLTYKNRLY FSVQARGETD REKLLLMYQT NDQIINGLFP LNKDLALEMA
ALLSQVEIGD FERPFSTPAG HVTNQCKVNQ TLKQVIEKFY PKRYRDGCSE EQLRQLCQRL
STRWMALRGH SAADCVRIYL TVARKWPFFG AKLFLAKPIT PSSLGSTFLW LAVHEDGLSL
LEYNSMRLIV SYVYKSLMTF GGYQDDFMVV INNTHSKDKP TEKLLFAMAK PKILEITLLI
ASYINNFHQQ KAAFHHLSAP ALLSAQTRGP QARMMGSQPL LSSSRPTKGP TLL
