Q6ISB3 (GRHL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Grainyhead-like protein 2 homolog

Alternative name(s):
Brother of mammalian grainyhead
Transcription factor CP2-like 3

Gene names

Name:	GRHL2
Synonyms:	BOM, TFCP2L3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	625 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May function as a transcription factor. Ref.5
Subunit structure	Homodimer, also forms heterodimers with GRHL1 or GRHL3.
Subcellular location	Nucleus.
Tissue specificity	Highly expressed in placenta, prostate, brain and kidney. Lower-level expression in a variety of epithelial tissues such as thymus, kidney, lung, salivary gland, mammary gland and digestive tract. Expressed in the cochlear. Ref.4 Ref.5
Involvement in disease	Deafness, autosomal dominant, 28 (DFNA28) [MIM:608641]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA28 is characterized by mild to moderate hearing loss across most frequencies that progresses to severe loss in the higher frequencies by the fifth decade. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4
Sequence similarities	Belongs to the grh/CP2 family. Grainyhead subfamily.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Deafness Non-syndromic deafness
Ligand	DNA-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	in utero embryonic development Inferred from electronic annotation. Source: Compara neural tube closure Inferred from electronic annotation. Source: Compara regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6ISB3-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q6ISB3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-16: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 625	625	Grainyhead-like protein 2 homolog		PRO_0000227994
Regions
	Region	1 – 93	93	Transcription activation
Natural variations
	Alternative sequence	1 – 16	16	Missing in isoform 2.		VSP_017642
	Natural variant	415	1	V → I. Corresponds to variant rs3779617 [ dbSNP | Ensembl ].		VAR_049293
Experimental info
	Sequence conflict	53	1	S → I in BAB14699. Ref.1
	Sequence conflict	430	1	R → Q in BAB14699. Ref.1
	Sequence conflict	436	1	K → N in BAB14699. Ref.1
	Sequence conflict	561	1	K → M in BAB14699. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 147CF33798248BB6	FASTA	625	71,105
	10 20 30 40 50 60 MSQESDNNKR LVALVPMPSD PPFNTRRAYT SEDEAWKSYL ENPLTAATKA MMSINGDEDS 70 80 90 100 110 120 AAALGLLYDY YKVPRDKRLL SVSKASDSQE DQEKRNCLGT SEAQSNLSGG ENRVQVLKTV 130 140 150 160 170 180 PVNLSLNQDH LENSKREQYS ISFPESSAII PVSGITVVKA EDFTPVFMAP PVHYPRGDGE 190 200 210 220 230 240 EQRVVIFEQT QYDVPSLATH SAYLKDDQRS TPDSTYSESF KDAATEKFRS ASVGAEEYMY 250 260 270 280 290 300 DQTSSGTFQY TLEATKSLRQ KQGEGPMTYL NKGQFYAITL SETGDNKCFR HPISKVRSVV 310 320 330 340 350 360 MVVFSEDKNR DEQLKYWKYW HSRQHTAKQR VLDIADYKES FNTIGNIEEI AYNAVSFTWD 370 380 390 400 410 420 VNEEAKIFIT VNCLSTDFSS QKGVKGLPLM IQIDTYSYNN RSNKPIHRAY CQIKVFCDKG 430 440 450 460 470 480 AERKIRDEER KQNRKKGKGQ ASQTQCNSSS DGKLAAIPLQ KKSDITYFKT MPDLHSQPVL 490 500 510 520 530 540 FIPDVHFANL QRTGQVYYNT DDEREGGSVL VKRMFRPMEE EFGPVPSKQM KEEGTKRVLL 550 560 570 580 590 600 YVRKETDDVF DALMLKSPTV KGLMEAISEK YGLPVEKIAK LYKKSKKGIL VNMDDNIIEH 610 620 YSNEDTFILN MESMVEGFKV TLMEI
	Isoform 2 [UniParc]. Checksum: E43F12B929E3473D	FASTA	609	69,322
	10 20 30 40 50 60 MPSDPPFNTR RAYTSEDEAW KSYLENPLTA ATKAMMSING DEDSAAALGL LYDYYKVPRD 70 80 90 100 110 120 KRLLSVSKAS DSQEDQEKRN CLGTSEAQSN LSGGENRVQV LKTVPVNLSL NQDHLENSKR 130 140 150 160 170 180 EQYSISFPES SAIIPVSGIT VVKAEDFTPV FMAPPVHYPR GDGEEQRVVI FEQTQYDVPS 190 200 210 220 230 240 LATHSAYLKD DQRSTPDSTY SESFKDAATE KFRSASVGAE EYMYDQTSSG TFQYTLEATK 250 260 270 280 290 300 SLRQKQGEGP MTYLNKGQFY AITLSETGDN KCFRHPISKV RSVVMVVFSE DKNRDEQLKY 310 320 330 340 350 360 WKYWHSRQHT AKQRVLDIAD YKESFNTIGN IEEIAYNAVS FTWDVNEEAK IFITVNCLST 370 380 390 400 410 420 DFSSQKGVKG LPLMIQIDTY SYNNRSNKPI HRAYCQIKVF CDKGAERKIR DEERKQNRKK 430 440 450 460 470 480 GKGQASQTQC NSSSDGKLAA IPLQKKSDIT YFKTMPDLHS QPVLFIPDVH FANLQRTGQV 490 500 510 520 530 540 YYNTDDEREG GSVLVKRMFR PMEEEFGPVP SKQMKEEGTK RVLLYVRKET DDVFDALMLK 550 560 570 580 590 600 SPTVKGLMEA ISEKYGLPVE KIAKLYKKSK KGILVNMDDN IIEHYSNEDT FILNMESMVE GFKVTLMEI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta.
[2]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
[4]	"Mutation of a transcription factor, TFCP2L3, causes progressive autosomal dominant hearing loss, DFNA28." Peters L.M., Anderson D.W., Griffith A.J., Grundfast K.M., San Agustin T.B., Madeo A.C., Friedman T.B., Morell R.J. Hum. Mol. Genet. 11:2877-2885(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN DFNA28, TISSUE SPECIFICITY.
[5]	"A highly conserved novel family of mammalian developmental transcription factors related to Drosophila grainyhead." Wilanowski T., Tuckfield A., Cerruti L., O'Connell S., Saint R., Parekh V., Tao J., Cunningham J.M., Jane S.M. Mech. Dev. 114:37-50(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH GRHL1.
[6]	"The identification and characterization of human sister-of-mammalian grainyhead (SOM) expands the grainyhead-like family of developmental transcription factors." Ting S.B., Wilanowski T., Cerruti L., Zhao L.L., Cunningham J.M., Jane S.M. Biochem. J. 370:953-962(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GRHL3.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK023844 mRNA. Translation: BAB14699.1. CH471060 Genomic DNA. Translation: EAW91834.1. BC069618 mRNA. Translation: AAH69618.1. BC069633 mRNA. Translation: AAH69633.1. BC069638 mRNA. Translation: AAH69638.1. BC129822 mRNA. Translation: AAI29823.1. BC129823 mRNA. Translation: AAI29824.1.
IPI	IPI00016576. IPI00736700.
RefSeq	NP_079191.2. NM_024915.3.
UniGene	Hs.661088.
3D structure databases
ProteinModelPortal	Q6ISB3.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6ISB3. 1 interaction.
STRING	9606.ENSP00000251808.
PTM databases
PhosphoSite	Q6ISB3.
Polymorphism databases
DMDM	74736618.
Proteomic databases
PaxDb	Q6ISB3.
PRIDE	Q6ISB3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000251808; ENSP00000251808; ENSG00000083307. ENST00000395927; ENSP00000379260; ENSG00000083307.
GeneID	79977.
KEGG	hsa:79977.
UCSC	uc010mbu.3. human.
Organism-specific databases
CTD	79977.
GeneCards	GC08P102575.
HGNC	HGNC:2799. GRHL2.
HPA	HPA004820.
MIM	608576. gene. 608641. phenotype.
neXtProt	NX_Q6ISB3.
Orphanet	90635. Autosomal dominant nonsyndromic sensorineural deafness type DFNA.
PharmGKB	PA27270.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG241458.
HOGENOM	HOG000220859.
HOVERGEN	HBG054154.
InParanoid	Q6ISB3.
KO	K09275.
OMA	KREQYSA.
OrthoDB	EOG4FBHSN.
PhylomeDB	Q6ISB3.
Gene expression databases
Bgee	Q6ISB3.
CleanEx	HS_GRHL2.
Genevestigator	Q6ISB3.
Family and domain databases
InterPro	IPR007604. CP2. [Graphical view]
Pfam	PF04516. CP2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	79977.
NextBio	70005.
SOURCE	Search...

Entry information

Entry name

GRHL2_HUMAN

Accession

Primary (citable) accession number: Q6ISB3
Secondary accession number(s): A1L303, Q6NT03, Q9H8B8

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 21, 2006
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 80 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.